Reactions of aromatic substrates with base-activated hydrosilanes-silylations and reductive cleavage

ABSTRACT

The present invention describes chemical systems and methods for reducing C—O, C—N, and C—S bonds, said system comprising a mixture of (a) at least one organosilane and (b) at least one strong base, said system being substantially free of a transition-metal compound, and said system optionally comprising at least one molecular hydrogen donor compound, molecular hydrogen, or both.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Patent Application Ser. Nos.61/708,931, filed Oct. 2, 2012, 61/818,573, filed May 2, 2013, and61/865,870, filed Aug. 14, 2013, the contents of each of which isincorporated by reference in its entirety for all purposes.

TECHNICAL FIELD

One aspect of the present invention is directed at processing materialsderived from biomass, including biomass (e.g, lignin, sugar), biomassliquifaction, biopyrolysis oil, black liquor, coal, coal liquifaction,natural gas, or petroleum process streams. In this way, the presentinvention is directed to systems and methods for reductively cleavingC—O, C—N, and C—S bonds in aromatic compounds, such as those found insuch process streams. In another aspect, the present invention is alsodirected at methods for silylating substrates comprising aromaticmoieties.

BACKGROUND

In the past few decades, the growing demand for energy combined withdeclining fossil fuel reserves has created a tremendous surge ininterest for efficient manufacturing of fuels and bulk chemicals fromrenewable bioresources. The natural heterobiopolymer lignin hasdeveloped into a major target for cost-efficient biomass conversionbecause the repeating aromatic ether structural units could offer highenergy content products and potential access to useful derivatives forfine chemical applications. However, at present, utilization of ligninis clearly limited since current technology does not allow for efficientdecomposition into its constituent building blocks with the desiredselectivity. One of the major challenges associated with such a processis the need to reductively cleave the different types of strong aromaticC—O bonds present in lignin (FIG. 1), which is also a relevant problemfor the liquefaction of coal.

Additional challenges are faced in the processing of coal and petroleumproducts, where increasing environmental regulations require the virtualelimination of sulfur from feedstreams. Combustion of sulfur leads tosulfur oxides with are environmentally undesirable in their own rights,but also tend to poison precious metal catalysts used, for example, incatalytic converters. There is a high interest in technologies which notonly depolymerize biomass, but which act to reduce or eliminate residualsulfur from these feedstock matrices.

Ni catalysts are known to provide selective reductive transformationsinvolving aryl-oxygen bonds, but only at loadings of 5-20%, and at theselevels the use of Ni and other transition-metal catalysts areproblematic, both from an economic and environmental perspective.Further, such catalysts are not reported to be useful on C—N or C—Sbonds. And while it would be beneficial to have a general methodologyfor aromatic C—O bond cleavage that does not employ nickel or othertransition metal catalysts, the only known alternative approaches formetal free ether cleavage at relatively low temperatures rely on excessalkali metals or electrocatalytic processes that tend to be costly,unsustainable and impractical.

Separately, the ability to silylate organic moieties has attractedsignificant attention in recent years, owing to the utility of thesilylated materials in their own rights, or as intermediates for otherimportant materials used, for example, in agrichemical, pharmaceutical,and electronic material applications. Further, the ability tofunctionalize polynuclear aromatic compounds with organosilanes providesopportunities to take advantage of the interesting properties of thesematerials.

Historically, the silylation of aromatic compounds has been achieved viafree radical processes involving thermally, photochemically, or byotherwise derived radical sources. More recently, the transition metalmediated aromatic C—H silylation has been described, with differentsystems described based on, for example, Co, Rh, Ir, Fe, Ru, Os, Ni, Pd,and Pt catalysts. But for certain electronic applications, the presenceof even low levels of such residues can adversely affect the performanceof the silylated materials. Similarly, in certain pharmaceuticalapplications, limits on residual transition metals are fairly strict,and the ability to avoid them entirely offers benefits duringpost-synthesis work-up.

The present invention is directed at solving at least some of theproblems in both of these areas.

SUMMARY

Various embodiments of the present invention provide chemical systemsfor reducing C—O, C—N, and C—S bonds, each system comprising a mixtureof (a) at least one organosilane and (b) at least one strong base, saidsystem being substantially free of a transition-metal compound, and saidsystem optionally comprising at least one molecular hydrogen donorcompound, molecular hydrogen, or both.

Other embodiments provide methods of reducing C—X bonds in a an organicsubstrate, where X is O, N, or S, each method comprising contacting aquantity of the substrate comprising at least one C—O, C—N, or C—S bondwith a chemical system comprising a mixture of (a) at least oneorganosilane and (b) at least one strong base, under conditionssufficient to reduce the C—X bonds of at least a portion of the quantityof the substrate; wherein said chemical system is substantially free ofa transition-metal compound, and said chemical system optionallycomprising at least one molecular hydrogen donor compound, molecularhydrogen, or both.

Various other embodiments of the present invention provide systems forsilylating organic compounds, each system comprising a mixture of (a) atleast one organosilane and (b) at least one strong base, said systembeing optionally free of a transition-metal compound.

Other embodiments provide methods, each method comprising contacting anorganic substrate comprising an aromatic moiety with a mixture of (a) atleast one organosilane and (b) at least one strong base, underconditions sufficient to silylate the substrate; wherein said mixtureand substrate are optionally free of a transition-metal compound.

BRIEF DESCRIPTION OF THE DRAWINGS

The present application is further understood when read in conjunctionwith the appended drawings. For the purpose of illustrating the subjectmatter, there are shown in the drawings exemplary embodiments of thesubject matter; however, the presently disclosed subject matter is notlimited to the specific methods, devices, and systems disclosed. Inaddition, the drawings are not necessarily drawn to scale. In thedrawings:

FIGS. 1A and 1B illustrate examples of C—O bonds such as are present inhardwood lignins. FIG. 1C illustrates some of the model compoundsdiscussed in this application for critical C—O linkages.

FIG. 2 shows the EPR spectrum of dibenzofuran, Et₃SiH and KOt-Bureaction mixture in toluene, as described in Example 5.8. The samesignal is observed without dibenzofuran added.

FIGS. 3A and 3B illustrate examples of some of the reactions availableby the methods described herein.

FIG. 4-17 are ¹H and ¹³C-NMR spectra or HSQC spectra of some of thecompounds prepared by the methods described herein. Unless otherwisestates, spectra were taken for compounds dissolved in CDCl₃ at 300 MHz(¹H) and 126 MHz (¹³C). Peaks marked with asterisks are deemed to beassociated with impurities in the respective sample.

FIG. 4 are (A)¹H and (B)¹³C-NMR spectra of toluene and itstriethylsilylation products.

FIG. 5 are (A)¹H and (B)¹³C-NMR spectra of mesitylene and itstriethylsilylation product.

FIG. 6 are (A)¹H and (B)¹³C-NMR spectra of o-triethylsilyldiphenylether.

FIG. 7 are the HSQC spectra of (A) 2-methoxynaphthalene and (B) theproduct of its reaction with triethylsilane, as described in Example6.2.2; characterized as triethyl-(3-methoxynaphthalen-2-yl)silane.

FIGS. 8A and B are the HSQC spectra of two of the products of thereaction between diphenyl ether and diethyl silane, as described inExample 6.2.3.

FIG. 9 are the HSQC spectra of (A) thioanisole (B) the product of itsreaction with triethylsilane, as described in Example 6.2.4.

FIG. 10 is the HSQC spectra of the reaction product of N-methylindolewith triethylsilane, as described in Example 6.3.1, characterized as1-methyl-2-(triethylsilyl)-1H-indole

FIG. 11 is the HSQC spectra of the reaction product of N-methylindolewith triethylsilane, as described in Example 6.3.2, characterized as1-methyl-3-(triethylsilyl)-1H-indole.

FIG. 12 is the HSQC spectra of the reaction product of1-methyl-1H-pyrrolo[2,3-b]pyridine with triethylsilane, as described inExample 6.3.6, characterized as1-methyl-2-(triethylsilyl)-1H-pyrrolo[2,3-b]pyridine.

FIG. 13 is the HSQC spectra of the reaction product of1,2-dimethylindole with triethylsilane, as described in Example 6.3.7.

FIG. 14 is the HSQC spectra of the reaction product of 1-phenylpyrrolewith triethylsilane, as described in Example 6.3.9, characterized as9,9-diethyl-9H-benzo[d]pyrrolo[1,2-a][1,3]azasilole.

FIG. 15 is the HSQC spectra of the reaction product of benzofuran withtriethylsilane, as described in Example 6.3.10, characterized asbenzofuran-2-yltriethylsilane.

FIG. 16A-B are the HSQC spectra of (A) benzothiophene and (B) theproduct of its reaction with triethylsilane, as described in Example6.3.11, characterized as benzo[b]thiophen-3-yltriethylsilane.

FIG. 17 is the HSQC spectra of the reaction product of dibenzothiophenewith triethylsilane, as described in Example 6.3.13, characterized as4-(triethylsilyl)dibenzopthiophene.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The present invention is founded on a set of reactions, each of whichrelies on simple mixtures of organosilanes and strong bases, whichtogether form in situ reductive systems (the structure and nature ofwhich is still completely unknown) able to activate C—O, C—N, and C—Sbonds in the liquid phase, or silylate aromatic substrates, without thenecessary presence of transition metal catalysts, UV radiation orelectrical discharges. These reactions are relevant as an importantadvance in developing practical methods for the decomposition ofbiomass-based feedstreams into aromatic feedstocks and fuels.Importantly this reaction is of great interest since it produces onlyenvironmentally benign silicates as the byproduct and avoids toxic metalwaste streams as would be observed with nearly all other approachesproposed in the literature towards this end. In the case of sulfurcompounds, a double C—S activation protocol has been observed under thereaction conditions leading to a formal removal of the sulfur atom fromthe substrate molecule. This remarkable observation is also relevant tothe desulfurization of sulfur-containing contaminants in crude oilstreams which is of great interest and high value. In other aspects,these reactions are relevant as an important advance in developingpractical methods for the preparation of silylated products importantfor pharmaceutical and electronics applications. The remarkable facilityand regiospecificity exhibited by at least some of these systemsprovides a useful tool in the kit of chemists in these fields.

The present invention may be understood more readily by reference to thefollowing description taken in connection with the accompanying Figuresand Examples, all of which form a part of this disclosure. It is to beunderstood that this invention is not limited to the specific products,methods, conditions or parameters described or shown herein, and thatthe terminology used herein is for the purpose of describing particularembodiments by way of example only and is not intended to be limiting ofany claimed invention. Similarly, unless specifically otherwise stated,any description as to a possible mechanism or mode of action or reasonfor improvement is meant to be illustrative only, and the inventionherein is not to be constrained by the correctness or incorrectness ofany such suggested mechanism or mode of action or reason forimprovement. Throughout this text, it is recognized that thedescriptions refer to compositions and methods of making and using saidcompositions. That is, where the disclosure describes or claims afeature or embodiment associated with a composition or a method ofmaking or using a composition, it is appreciated that such a descriptionor claim is intended to extend these features or embodiment toembodiments in each of these contexts (i.e., compositions, methods ofmaking, and methods of using).

In the present disclosure the singular forms “a,” “an,” and “the”include the plural reference, and reference to a particular numericalvalue includes at least that particular value, unless the contextclearly indicates otherwise. Thus, for example, a reference to “amaterial” is a reference to at least one of such materials andequivalents thereof known to those skilled in the art, and so forth.

When a value is expressed as an approximation by use of the descriptor“about,” it will be understood that the particular value forms anotherembodiment. In general, use of the term “about” indicates approximationsthat can vary depending on the desired properties sought to be obtainedby the disclosed subject matter and is to be interpreted in the specificcontext in which it is used, based on its function. The person skilledin the art will be able to interpret this as a matter of routine. Insome cases, the number of significant figures used for a particularvalue may be one non-limiting method of determining the extent of theword “about.” In other cases, the gradations used in a series of valuesmay be used to determine the intended range available to the term“about” for each value. Where present, all ranges are inclusive andcombinable. That is, references to values stated in ranges include everyvalue within that range.

It is to be appreciated that certain features of the invention whichare, for clarity, described herein in the context of separateembodiments, may also be provided in combination in a single embodiment.That is, unless obviously incompatible or specifically excluded, eachindividual embodiment is deemed to be combinable with any otherembodiment(s) and such a combination is considered to be anotherembodiment. Conversely, various features of the invention that are, forbrevity, described in the context of a single embodiment, may also beprovided separately or in any sub-combination. Finally, while anembodiment may be described as part of a series of steps or part of amore general structure, each said step may also be considered anindependent embodiment in itself, combinable with others.

The transitional terms “comprising,” “consisting essentially of,” and“consisting” are intended to connote their generally in acceptedmeanings in the patent vernacular; that is, (i) “comprising,” which issynonymous with “including,” “containing,” or “characterized by,” isinclusive or open-ended and does not exclude additional, unrecitedelements or method steps; (ii) “consisting of” excludes any element,step, or ingredient not specified in the claim; and (iii) “consistingessentially of” limits the scope of a claim to the specified materialsor steps “and those that do not materially affect the basic and novelcharacteristic(s)” of the claimed invention. Embodiments described interms of the phrase “comprising” (or its equivalents), also provide, asembodiments, those which are independently described in terms of“consisting of” and “consisting essentially of” For those embodimentsdirected to the reductive cleavage of aromatic C—O, C—N, and C—S bondsand provided in terms of “consisting essentially of,” the basic andnovel characteristic(s) is the operability of the methods (or thesystems used in such methods or the compositions derived therefrom) as atransition metal-free method of effecting the reductive cleavage of C—O,C—N, or C—S bonds. For those embodiments directed to silylationreactions provided in terms of “consisting essentially of,” the basicand novel characteristic(s) is the facile operability of the methods (orthe systems used in such methods or the compositions derived therefrom)to silylate aromatic organic moieties.

When a list is presented, unless stated otherwise, it is to beunderstood that each individual element of that list, and everycombination of that list, is a separate embodiment. For example, a listof embodiments presented as “A, B, or C” is to be interpreted asincluding the embodiments, “A,” “B,” “C,” “A or B,” “A or C,” “B or C,”or “A, B, or C.”

Throughout this specification, words are to be afforded their normalmeaning, as would be understood by those skilled in the relevant art.However, so as to avoid misunderstanding, the meanings of certain termswill be specifically defined or clarified.

The term “alkyl” as used herein refers to a linear, branched, or cyclicsaturated hydrocarbon group typically although not necessarilycontaining 1 to about 24 carbon atoms, preferably 1 to about 12 carbonatoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,t-butyl, octyl, decyl, and the like, as well as cycloalkyl groups suchas cyclopentyl, cyclohexyl and the like. Generally, although again notnecessarily, alkyl groups herein contain 1 to about 12 carbon atoms. Theterm “lower alkyl” intends an alkyl group of 1 to 6 carbon atoms, andthe specific term “cycloalkyl” intends a cyclic alkyl group, typicallyhaving 4 to 8, preferably 5 to 7, carbon atoms. The term “substitutedalkyl” refers to alkyl groups substituted with one or more substituentgroups, and the terms “heteroatom-containing alkyl” and “heteroalkyl”refer to alkyl groups in which at least one carbon atom is replaced witha heteroatom. If not otherwise indicated, the terms “alkyl” and “loweralkyl” include linear, branched, cyclic, unsubstituted, substituted,and/or heteroatom-containing alkyl and lower alkyl groups, respectively.

The term “alkylene” as used herein refers to a difunctional linear,branched, or cyclic alkyl group, where “alkyl” is as defined above.

The term “alkenyl” as used herein refers to a linear, branched, orcyclic hydrocarbon group of 2 to about 24 carbon atoms containing atleast one double bond, such as ethenyl, n-propenyl, isopropenyl,n-butenyl, isobutenyl, octenyl, decenyl, tetradecenyl, hexadecenyl,eicosenyl, tetracosenyl, and the like. Preferred alkenyl groups hereincontain 2 to about 12 carbon atoms. The term “lower alkenyl” intends analkenyl group of 2 to 6 carbon atoms, and the specific term“cycloalkenyl” intends a cyclic alkenyl group, preferably having 5 to 8carbon atoms. The term “substituted alkenyl” refers to alkenyl groupssubstituted with one or more substituent groups, and the terms“heteroatom-containing alkenyl” and “heteroalkenyl” refer to alkenylgroups in which at least one carbon atom is replaced with a heteroatom.If not otherwise indicated, the terms “alkenyl” and “lower alkenyl”include linear, branched, cyclic, unsubstituted, substituted, and/orheteroatom-containing alkenyl and lower alkenyl groups, respectively.

The term “alkenylene” as used herein refers to a difunctional linear,branched, or cyclic alkenyl group, where “alkenyl” is as defined above.

The term “alkynyl” as used herein refers to a linear or branchedhydrocarbon group of 2 to about 24 carbon atoms containing at least onetriple bond, such as ethynyl, n-propynyl, and the like. Preferredalkynyl groups herein contain 2 to about 12 carbon atoms. The term“lower alkynyl” intends an alkynyl group of 2 to 6 carbon atoms. Theterm “substituted alkynyl” refers to an alkynyl group substituted withone or more substituent groups, and the terms “heteroatom-containingalkynyl” and “heteroalkynyl” refer to alkynyl in which at least onecarbon atom is replaced with a heteroatom. If not otherwise indicated,the terms “alkynyl” and “lower alkynyl” include a linear, branched,unsubstituted, substituted, and/or heteroatom-containing alkynyl andlower alkynyl group, respectively.

The term “alkoxy” as used herein intends an alkyl group bound through asingle, terminal ether linkage; that is, an “alkoxy” group may berepresented as —O-alkyl where alkyl is as defined above. A “loweralkoxy” group intends an alkoxy group containing 1 to 6 carbon atoms.Analogously, “alkenyloxy” and “lower alkenyloxy” respectively refer toan alkenyl and lower alkenyl group bound through a single, terminalether linkage, and “alkynyloxy” and “lower alkynyloxy” respectivelyrefer to an alkynyl and lower alkynyl group bound through a single,terminal ether linkage.

The term “aromatic” refers to the ring moieties which satisfy the Hückel4n+2 rule for aromaticity, and includes both aryl (i.e., carbocyclic)and heteroaryl (also called heteroaromatic) structures, including aryl,aralkyl, alkaryl, heteroaryl, heteroaralkyl, or alk-heteroaryl moieties.

The term “aryl” as used herein, and unless otherwise specified, refersto an aromatic substituent or structure containing a single aromaticring or multiple aromatic rings that are fused together, directlylinked, or indirectly linked (such that the different aromatic rings arebound to a common group such as a methylene or ethylene moiety). Unlessotherwise modified, the term “aryl” refers to carbocyclic structures.Preferred aryl groups contain 5 to 24 carbon atoms, and particularlypreferred aryl groups contain 5 to 14 carbon atoms. Exemplary arylgroups contain one aromatic ring or two fused or linked aromatic rings,e.g., phenyl, naphthyl, biphenyl, diphenylether, diphenylamine,benzophenone, and the like. “Substituted aryl” refers to an aryl moietysubstituted with one or more substituent groups, and the terms“heteroatom-containing aryl” and “heteroaryl” refer to aryl substituentsin which at least one carbon atom is replaced with a heteroatom, as willbe described in further detail infra.

The term “aryloxy” as used herein refers to an aryl group bound througha single, terminal ether linkage, wherein “aryl” is as defined above. An“aryloxy” group may be represented as —O-aryl where aryl is as definedabove. Preferred aryloxy groups contain 5 to 24 carbon atoms, andparticularly preferred aryloxy groups contain 5 to 14 carbon atoms.Examples of aryloxy groups include, without limitation, phenoxy,o-halo-phenoxy, m-halo-phenoxy, p-halo-phenoxy, o-methoxy-phenoxy,m-methoxy-phenoxy, p-methoxy-phenoxy, 2,4-dimethoxy-phenoxy,3,4,5-trimethoxy-phenoxy, and the like.

The term “alkaryl” refers to an aryl group with an alkyl substituent,and the term “aralkyl” refers to an alkyl group with an arylsubstituent, wherein “aryl” and “alkyl” are as defined above. Preferredalkaryl and aralkyl groups contain 6 to 24 carbon atoms, andparticularly preferred alkaryl and aralkyl groups contain 6 to 16 carbonatoms. Alkaryl groups include, for example, p-methylphenyl,2,4-dimethylphenyl, p-cyclohexylphenyl, 2, 7-dimethylnaphthyl,7-cyclooctylnaphthyl, 3-ethyl-cyclopenta-1,4-diene, and the like.Examples of aralkyl groups include, without limitation, benzyl,2-phenyl-ethyl, 3-phenyl-propyl, 4-phenyl-butyl, 5-phenyl-pentyl,4-phenylcyclohexyl, 4-benzylcyclohexyl, 4-phenylcyclohexylmethyl,4-benzylcyclohexylmethyl, and the like. The terms “alkaryloxy” and“aralkyloxy” refer to substituents of the formula —OR wherein R isalkaryl or aralkyl, respectively, as just defined.

The term “acyl” refers to substituents having the formula —(CO)-alkyl,—(CO)-aryl, or —(CO)-aralkyl, and the term “acyloxy” refers tosubstituents having the formula —O(CO)— alkyl, —O(CO)-aryl, or—O(CO)-aralkyl, wherein “alkyl,” “aryl, and “aralkyl” are as definedabove.

The terms “cyclic” and “ring” refer to alicyclic or aromatic groups thatmay or may not be substituted and/or heteroatom-containing, and that maybe monocyclic, bicyclic, or polycyclic. The term “alicyclic” is used inthe conventional sense to refer to an aliphatic cyclic moiety, asopposed to an aromatic cyclic moiety, and may be monocyclic, bicyclic,or polycyclic. The term “acyclic” refers to a structure in which adouble bond may or may not be contained within the ring structure.

The terms “halo,” “halide,” and “halogen” are used in the conventionalsense to refer to a chloro, bromo, fluoro, or iodo substituent.

“Hydrocarbyl” refers to univalent hydrocarbyl radicals containing 1 toabout 30 carbon atoms, preferably 1 to about 24 carbon atoms, mostpreferably 1 to about 12 carbon atoms, including linear, branched,cyclic, saturated, and unsaturated species, such as alkyl groups,alkenyl groups, aryl groups, and the like. The term “lower hydrocarbyl”intends a hydrocarbyl group of 1 to 6 carbon atoms, preferably 1 to 4carbon atoms, and the term “hydrocarbylene” intends a divalenthydrocarbyl moiety containing 1 to about 30 carbon atoms, preferably 1to about 24 carbon atoms, most preferably 1 to about 12 carbon atoms,including linear, branched, cyclic, saturated and unsaturated species.The term “lower hydrocarbylene” intends a hydrocarbylene group of 1 to 6carbon atoms. “Substituted hydrocarbyl” refers to hydrocarbylsubstituted with one or more substituent groups, and the terms“heteroatom-containing hydrocarbyl” and “heterohydrocarbyl” refer tohydrocarbyl in which at least one carbon atom is replaced with aheteroatom. Similarly, “substituted hydrocarbylene” refers tohydrocarbylene substituted with one or more substituent groups, and theterms “heteroatom-containing hydrocarbylene” and heterohydrocarbylene”refer to hydrocarbylene in which at least one carbon atom is replacedwith a heteroatom. Unless otherwise indicated, the term “hydrocarbyl”and “hydrocarbylene” are to be interpreted as including substitutedand/or heteroatom-containing hydrocarbyl and hydrocarbylene moieties,respectively.

The term “heteroatom-containing” as in a “heteroatom-containinghydrocarbyl group” refers to a hydrocarbon molecule or a hydrocarbylmolecular fragment in which one or more carbon atoms is replaced with anatom other than carbon, e.g., nitrogen, oxygen, sulfur, phosphorus orsilicon, typically nitrogen, oxygen or sulfur. Similarly, the term“heteroalkyl” refers to an alkyl substituent that isheteroatom-containing, the term “heterocyclic” refers to a cyclicsubstituent that is heteroatom-containing, the terms “heteroaryl” andheteroaromatic” respectively refer to “aryl” and “aromatic” substituentsthat are heteroatom-containing, and the like. It should be noted that a“heterocyclic” group or compound may or may not be aromatic, and furtherthat “heterocycles” may be monocyclic, bicyclic, or polycyclic asdescribed above with respect to the term “aryl.” Examples of heteroalkylgroups include alkoxyaryl, alkylsulfanyl-substituted alkyl, N-alkylatedamino alkyl, and the like. Examples of heteroaryl substituents includepyrrolyl, pyrrolidinyl, pyridinyl, quinolinyl, indolyl, pyrimidinyl,imidazolyl, 1,2,4-triazolyl, tetrazolyl, etc., and examples ofheteroatom-containing alicyclic groups are pyrrolidino, morpholino,piperazino, piperidino, etc.

By “substituted” as in “substituted hydrocarbyl,” “substituted alkyl,”“substituted aryl,” and the like, as alluded to in some of theaforementioned definitions, is meant that in the hydrocarbyl, alkyl,aryl, or other moiety, at least one hydrogen atom bound to a carbon (orother) atom is replaced with one or more non-hydrogen substituents.Examples of such substituents include, without limitation: functionalgroups referred to herein as “Fn,” such as halo, hydroxyl, sulfhydryl,C₁-C₂₄ alkoxy, C₂-C₂₄ alkenyloxy, C₂-C₂₄ alkynyloxy, C₅-C₂₄ aryloxy,C₆-C₂₄ aralkyloxy, C₆-C₂₄ alkaryloxy, acyl (including C₁-C₂₄alkylcarbonyl (—CO-alkyl) and C₆-C₂₄ arylcarbonyl (—CO-aryl)), acyloxy(—O-acyl, including C₂-C₂₄ alkylcarbonyloxy (—O—CO-alkyl) and C₆-C₂₄arylcarbonyloxy (—O—CO-aryl)), C₂-C₂₄ alkoxycarbonyl ((CO)—O-alkyl),C₆-C₂₄ aryloxycarbonyl (—(CO)—O-aryl), halocarbonyl (—CO)—X where X ishalo), C₂-C₂₄ alkylcarbonato (—O—(CO)—O-alkyl), C₆-C₂₄ arylcarbonato(—O—(CO)—O-aryl), carboxy (—COOH), carboxylato (—COO—), carbamoyl(—(CO)—NH₂), mono-(C₁-C₂₄ alkyl)-substituted carbamoyl (—(CO)NH(C₁-C₂₄alkyl)), di-(C₁-C₂₄ alkyl)-substituted carbamoyl (—(CO)—N(C₁-C₂₄alkyl)₂), mono-(C₁-C₂₄ haloalkyl)-substituted carbamoyl (—(CO)—NH(C₁-C₂₄alkyl)), di-(C₁-C₂₄ haloalkyl)-substituted carbamoyl (—(CO)—N(C₁-C₂₄alkyl)₂), mono-(C₅-C₂₄ aryl)-substituted carbamoyl (—(CO)—NH-aryl),di-(C₅-C₂₄ aryl) substituted carbamoyl (—(CO)—N(C₅-C₂₄ aryl)₂),di-N—(C₁-C₂₄ alkyl), N—(C₅-C₂₄ aryl)-substituted carbamoyl,thiocarbamoyl (—(CS)—NH₂), mono-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl(—(CO)—NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl(—(CO)—N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄ aryl) substituted thiocarbamoyl(—(CO)—NH-aryl), di-(C₅-C₂₄ aryl)-substituted thiocarbamoyl(—(CO)—N(C₅-C₂₄ aryl)₂), di-N—(C₁-C₂₄ alkyl), N—(C₅-C₂₄aryl)-substituted thiocarbamoyl, carbamido (—NH—(CO)—NH₂), cyano(—C≡N),cyanato (—O—C═N), thiocyanato (—S—C═N), formyl (—(CO)—H), thioformyl(—(CS)—H), amino (—NH₂), mono-(C₁-C₂₄ alkyl)-substituted amino,di-(C₁-C₂₄ alkyl)-substituted amino, mono-(C₅-C₂₄ aryl) substitutedamino, di-(C₅-C₂₄ aryl)-substituted amino, C₁-C₂₄ alkylamido(—NH—(CO)-alkyl), C₆-C₂₄ arylamido (—NH—(CO)-aryl), imino (—CR═NH whereR=hydrogen, C₁-C₂₄ alkyl, C5-C24 aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl,etc.), C₂-C₂₀ alkylimino (—CR═N(alkyl), where R=hydrogen, C₁-C₂₄ alkyl,C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), arylimino(—CR═N(aryl), where R=hydrogen, C₁-C₂₀ alkyl, C₅-C₂₄ aryl, C₆-C₂₄alkaryl, C₆-C₂₄ aralkyl, etc.), nitro (—NO₂), nitroso (—NO), sulfo(—SO₂OH), sulfonate (SO₂O—), C₁-C₂₄ alkylsulfanyl (—S-alkyl; also termed“alkylthio”), C₅-C₂₄ arylsulfanyl (—S-aryl; also termed “arylthio”),C₁-C₂₄ alkylsulfinyl (—(SO)-alkyl), C₅-C₂₄ arylsulfinyl (—(SO)-aryl),C₁-C₂₄ alkylsulfonyl (—SO₂-alkyl), C₁-C₂₄monoalkylaminosulfonyl-SO₂—N(H) alkyl), C₁-C₂₄dialkylaminosulfonyl-SO₂—N(alkyl)₂, C₅-C₂₄ arylsulfonyl (—SO₂-aryl),boryl (—BH₂), borono (—B(OH)₂), boronato (—B(OR)₂ where R is alkyl orother hydrocarbyl), phosphono (—P(O)(OH)₂), phosphonato (—P(O)(O)₂),phosphinato (P(O)(O—)), phospho (—PO₂), and phosphine (—PH₂); and thehydrocarbyl moieties C₁-C₂₄ alkyl (preferably C₁-C₁₂ alkyl, morepreferably C₁-C₆ alkyl), C₂-C₂₄ alkenyl (preferably C₂-C₁₂ alkenyl, morepreferably C₂-C₆ alkenyl), C₂-C₂₄ alkynyl (preferably C₂-C₁₂ alkynyl,more preferably C₂-C₆ alkynyl), C₅-C₂₄ aryl (preferably C₅-C₂₄ aryl),C₆-C₂₄ alkaryl (preferably C₆-C₁₆ alkaryl), and C₆-C₂₄ aralkyl(preferably C₆-C₁₆ aralkyl). Within these substituent structures, the“alkyl,” “alkylene,” “alkenyl,” “alkenylene,” “alkynyl,” “alkynylene,”“alkoxy,” “aromatic,” “aryl,” “aryloxy,” “alkaryl,” and “aralkyl”moieties may be optionally fluorinated or perfluorinated. Additionally,reference to alcohols, aldehydes, amines, carboxylic acids, ketones, orother similarly reactive functional groups also includes their protectedanalogs. For example, reference to hydroxy or alcohol also includesthose substituents wherein the hydroxy is protected by acetyl (Ac),benzoyl (Bz), benzyl (Bn, Bnl), β-Methoxyethoxymethyl ether (MEM),dimethoxytrityl, [bis-(4-methoxyphenyl)phenylmethyl] (DMT),methoxymethyl ether (MOM), methoxytrityl[(4-methoxyphenyl)diphenylmethyl, MMT), p-methoxybenzyl ether (PMB),methylthiomethyl ether, pivaloyl (Piv), tetrahydropyranyl (THP),tetrahydrofuran (THF), trityl (triphenylmethyl, Tr), silyl ether (mostpopular ones include trimethylsilyl (TMS), tert-butyldimethylsilyl(TBDMS), tri-iso-propylsilyloxymethyl (TOM), and triisopropylsilyl(TIPS) ethers), ethoxyethyl ethers (EE). Reference to amines alsoincludes those substituents wherein the amine is protected by a BOCglycine, carbobenzyloxy (Cbz), p-methoxybenzyl carbonyl (Moz or MeOZ),tert-butyloxycarbonyl (BOC), 9-fluorenylmethyloxycarbonyl (FMOC), acetyl(Ac), benzoyl (Bz), benzyl (Bn), carbamate, p-methoxybenzyl (PMB),3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), tosyl (Ts) group, orsulfonamide (Nosyl & Nps) group. Reference to substituent containing acarbonyl group also includes those substituents wherein the carbonyl isprotected by an acetal or ketal, acylal, or diathane group. Reference tosubstituent containing a carboxylic acid or carboxylate group alsoincludes those substituents wherein the carboxylic acid or carboxylategroup is protected by its methyl ester, benzyl ester, tert-butyl ester,an ester of 2,6-disubstituted phenol (e.g. 2,6-dimethylphenol,2,6-diisopropylphenol, 2,6-di-tert-butylphenol), a silyl ester, anorthoester, or an oxazoline.

By “functionalized” as in “functionalized hydrocarbyl,” “functionalizedalkyl,” “functionalized olefin,” “functionalized cyclic olefin,” and thelike, is meant that in the hydrocarbyl, alkyl, olefin, cyclic olefin, orother moiety, at least one hydrogen atom bound to a carbon (or other)atom is replaced with one or more functional groups such as thosedescribed herein and above. The term “functional group” is meant toinclude any functional species that is suitable for the uses describedherein. In particular, as used herein, a functional group wouldnecessarily possess the ability to react with or bond to correspondingfunctional groups on a substrate surface.

In addition, the aforementioned functional groups may, if a particulargroup permits, be further substituted with one or more additionalfunctional groups or with one or more hydrocarbyl moieties such as thosespecifically enumerated above. Analogously, the above-mentionedhydrocarbyl moieties may be further substituted with one or morefunctional groups or additional hydrocarbyl moieties such as thosespecifically enumerated.

“Optional” or “optionally” means that the subsequently describedcircumstance may or may not occur, so that the description includesinstances where the circumstance occurs and instances where it does not.For example, the phrase “optionally substituted” means that anon-hydrogen substituent may or may not be present on a given atom, and,thus, the description includes structures wherein a non-hydrogensubstituent is present and structures wherein a non-hydrogen substituentis not present.

The present invention includes embodiments related chemical systems andmethods for reducing C—O, C—N, and C—S bonds. Specific embodimentsprovide chemical systems for reducing C—O, C—N, and C—S bonds, eachsystem comprising a mixture of (a) at least one organosilane and (b) atleast one strong base; said system optionally comprising at least onemolecular hydrogen donor compound, molecular hydrogen, or both, and saidsystem preferably being substantially free of a transition-metalcompound. While certain embodiments provide that transition metals,including those capable of catalyzing silylation reactions, may bepresent within the systems or methods described herein at levelsnormally associated with such catalytic activity, the presence of suchmetals (either as catalysts or spectator compounds) is not required andin many cases is not desirable. As such, in preferred embodiments, thesystem and methods are “substantially free of transition-metalcompounds.” As used herein, the term “substantially free of atransition-metal compound” is intended to reflect that the system iseffective for its intended purpose of reducing C—O, C—N, and C—S bondseven in the absence of any exogenous (i.e., deliberately added orotherwise) transition-metal catalyst(s). Unless otherwise stated, then,the term “substantially free of a transition-metal compound” is definedto reflect that the total level of transition metal within the reducingsystem, independently or in the presence of organic substrate, is lessthan about 50 ppm, as measured by ICP-MS as described in Example 2below. Additional embodiments also provide that the concentration oftransition metals is less than about 100 ppm, 50 ppm, 30 ppm, 25 ppm, 20ppm, 15 ppm, 10 ppm, or 5 ppm to about 1 ppm or 0 ppm. As used herein,the term “transition metal” is defined to include Co, Rh, Ir, Fe, Ru,Os, Ni, Pd, Pt, Cu, or combinations thereof. In further specificindependent embodiments, the concentration of Ni, as measured by ICP-MS,is less than 25 ppm, less than 10 ppm, less than 5 ppm, or less than 1ppm.

Also, as used herein, the terms “reducing (as in C—O, C—N, and C—Sbonds)” or “reductive cleavage” refer to a chemical transformation wherethe O, N, or S moieties are replaced by less electronegative groups, forexample and including H, D, or Si.

While it may not be necessary to limit the system's exposure to waterand oxygen, in some embodiments, the chemical system and the methods aredone in an environment substantially free of water, oxygen, or bothwater and oxygen. Unless otherwise specified, the term “substantiallyfree of water” refers to levels of water less than about 500 ppm and“substantially free of oxygen” refers to oxygen levels corresponding topartial pressures less than 1 torr. Where stated, additional independentembodiments may provide that “substantially free of water” refers tolevels of water less than 1.5%, 1%, 0.5%, 1000 ppm, 500 ppm, 250 ppm,100 ppm, 50 ppm, 10 ppm, or 1 ppm and “substantially free of oxygen”refers to oxygen levels corresponding to partial pressures less than 50torr, 10 torr, 5 torr, 1 torr, 500 millitorr, 250 millitorr, 100millitorr, 50 millitorr, or 10 millitorr.

While not intending to be bound by the correctness of any proposedmechanism of interaction (especially since its role is yet unknown), itappears that the presence of hydrogen during the reducing process isimportant for the reductive cleavages to proceed, even if only to theextent that hydrogen appears to be generated during the reductionprocess (see infra), and its presence seems to improve (if not benecessary for) or its absence detracts from the reductive cleavagesdescribed herein. Interesting, the addition of molecular hydrogen donorcompounds also has a positive effect on the system in reducing C—O, C—N,and C—S bonds (see, e.g., Example 5.9, Table 2, Entry 18), while hydridedonors (including, e.g., borohydrides, aluminum or tin hydrides)apparently do not (e.g., see Example 5.12, Table 4, Entries 3, 5-7).Exemplary hydrogen donor compounds may include compounds such as1,3-cyclohexadiene, 1,4-cyclohexadiene, 1,2-cyclohexadiene,1,4-cyclohexadiene 1,2-dihydronaphthalene, 1,4-dihydronaphthalene,1,2-dihydroquinoline, 3,4-dihydroquinoline, 9,10-dihydroanthracene, ortetralin.

The mechanism by which the system and methods operate is not yetunderstood, and the inventors are not bound by the correctness orincorrectness of any particular theory as to mode of mechanism, but someobservations point to the possibility that the active reductant siliconspecies may be an organosilicate. Further, as described herein, thereductive cleavage is also often accompanied by the presence ofsilylation of the organic substrate, though at this point it is unclearwhether such species are intermediates, co-products, or both. But itdoes appear that the presence of hydrogen donors and hydrogen itselfplays in an important role in determining the extent of conversion andthe relative amounts of cleavage and silylation; see Example 5.9, Table2.

The importance of hydrogen or hydrogen donors can be seen in the resultsof a series of experiments in which the presence of hydrogen or hydrogendonors were specifically manipulated. As described in Example 3 below,many experiments were conducted in sealed glass containers. Headspaceanalysis of these sealed reaction mixtures indicated the formation ofH₂. To a certain its importance, additional experiments were conductedwhere the reaction was opened to an atmosphere of argon, whereupon adramatic decrease in reductive cleavage product formation occurred thatwas offset by increased silylation (Example 5.9, Table 2, compareEntries 4-6). This result suggested that dihydrogen might be importantto prevent decomposition of the active reducing species. In a search tofurther modulate the selectivity by shutting down radical pathways,experiments were conducted using 1,4-cyclohexadiene as a non-polarhydrogen donor co-solvent, resulting in the exclusive formation of 2with 95% yield (Example 5.9, Table 2, Entry 18). These resultsdemonstrate the ability to tune the selectivity of the reaction byaltering the reaction conditions.

As used herein, the term “organosilane” refers to a compound or reagenthaving at least one silicon-hydrogen (Si—H) bond. The organosilane mayfurther contain a silicon-carbon, a silicon-oxygen, a silicon-nitrogenbond, or a combination thereof, and may be monomeric, or containedwithin an oligomeric or polymeric framework, including being tethered toa heterogeneous or homogeneous support structure. In certainembodiments, these organosilane may comprise at least one compound ofFormula (I) or Formula (II):(R)_(4-m)Si(H)_(m)(I)R—[—SiH(R)—O—]_(n)—R  (II)where: m is 1, 2, or 3, preferably 1;

n is in a range of from about 5 to about 500, from about 10 to about 100or from about 25 to about 50; and

R is independently optionally substituted C₁₋₁₂ alkyl or heteroalkyl,C₅₋₂₀ aryl or heteroaryl, C₆₋₃₀ alkaryl or heteroalkaryl, C₆₋₃₀ aralkylor heteroaralkyl, —O—C₁₋₁₂ alkyl or heteroalkyl, —O—C₅₋₂₀ aryl orheteroaryl, —O—C₆₋₃₀ alkaryl or heteroalkaryl, —O—C₆₋₃₀ aralkyl orheteroaralkyl, and, if substituted, the substituents may be phosphonato,phosphoryl, phosphanyl, phosphino, sulfonato, C₁-C₂₀ alkylsulfanyl,C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfonyl, C₅-C₂₀ arylsulfonyl, C₁-C₂₀alkylsulfinyl, C₅-C₂₀ arylsulfinyl, sulfonamido, amino, amido, imino,nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₂-C₂₀alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, carboxyl, carboxylato, mercapto,formyl, C₁-C₂₀ thioester, cyano, cyanato, thiocyanato, isocyanate,thioisocyanate, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl,siloxazanyl, boronato, boryl, or halogen, or a metal-containing ormetalloid-containing group, where the metalloid is Sn or Ge, where thesubstituents may optionally provide a tether to an insoluble orsparingly soluble support media comprising alumina, silica, or carbon.Exemplary, non-limiting organosilanes include (R)₃SiH, where R is C₁₋₆alkyl, particularly triethylsilane and tributylsilane, mixed aryl alkylsilanes, such as PhMe₂SiH, and polymeric materials, such aspolymethylhydrosiloxane (PMHS).

As used herein, the term “strong base” refers to a compound having astrong affinity for hydrogen atoms especially, but not only, innon-aqueous media. In specific independent embodiments, the at least onestrong base comprises an alkali or alkaline metal hydride or alkoxide.It should be appreciated, then, that this definition is not strictlylimited to the classic conjugate acid-base model—since the conjugateacid of hydride would be dihydrogen. One measure of this “strongaffinity” may be that the strong base, if reacted with water, wouldreact to the practically complete formation of hydroxide therefrom.Other “strong bases” may be considered as including alkyl lithiumcompounds or amide ions, for example potassium bis(trimethylsilyl)amide.

There appears to be a hierarchy of activity related to the counterion ofthe strong base, such that the use of cesium and potassium hydrides andalkoxides are preferred. Exemplary hydrides useful in the presentinvention include potassium hydride. Similarly, the effect oftemperature on the effectiveness of reaction with hydrides may be seenin Example 5.9, Table 2, entries 13 and 24, where the reaction ofdibenzofuran with KH conducted at 100° C. results in low conversionrates and low levels of formation of the mono-cleaved product,biphenyl-2-ol, whereas conducting a similar experiment at 165° C.resulted in essentially quantitative conversion to predominantly thatproduct.

Useful alkoxides include those comprising a C₁₋₁₂ linear or branchedalkyl moietird or a C₅₋₁₀ aromatic or heteroaromatic moieties, forexamples methoxide, ethoxide, propoxide, butoxide, 2-ethyl-hexyloxide,or benzyloxide. Each of these appears to give comparable reactivity(see, e.g., Example 5.9, Table 2, compare Entries 17, 25-26, and 28).Further, the choice of the counter cation also impacts the effectivenessof the activity of the chemical system, such that potassium or cesiumalkoxides are preferred. More specifically, potassium methoxide,ethoxide, and tert-butoxide and cesium 2-ethyl-hexyl alkoxide have beenshown to be particularly effective in this role. By comparison, thereaction of Et₃SiH with lithium or sodium tert-butoxide provides noconversion of dibenzofuran to the bisphenyl-2-ol (see, e.g., Example5.9, Table 2, Entries 29-31) suggesting that the counter ion plays acritical role in the generation of the active reductant species and,possibly, in activation of the substrate ether. Similarly, conductingreactions with potassium tert-butoxide in the presence of sufficient18-crown-6 to act as a potassium chelator resulted in nearly completeinhibition of the reaction (Table 4, Example 5.12, Entry 2).

While the relative amounts of organosilane and strong base is notbelieved to be particularly important, so long as both are present insufficient quantities, in certain embodiments, the organosilane and theat least one strong base are present together at a molar ratio, withrespect to one another, in a range of from about 20:1 to about 1:2. Inother embodiments, these ratios may be on the order of about 5:1 toabout 1:2, from about 3:1 to about 1:3, or from about 3:2 to about 2:3.In still other embodiments, the system has been shown to be effectivewhen the organosilane is used as a solvent for the reductions. Also, theintended organic substrate for the chemical reductions may be used asthe solvent. In certain embodiments, the chemical system may be seen asincluding an organic substrate containing oxygen, nitrogen, sulfur, or acombination thereof, including where the organic substrate is containedwithin a biomass (e.g, lignin, sugar), biomass liquifaction,biopyrolysis oil, black liquor, coal, coal liquifaction, natural gas, orpetroleum batch or process stream.

The reducing system may further comprise a solvent other than theorganosilane. As shown thus far, preferred solvents appear to be thosethat are aprotic. Also, the reductive cleavage reactions appear also tofavor higher temperatures, though are not necessarily limited to thisconstraint (for example, cesium ethyl-hexyl alkoxide has been shown toreduce C—O bonds with triethylsilane at ambient room temperature).Accordingly, solvents having boiling points (at one atmosphere pressure)in a range bounded at the lower end by a value of about 25° C., 50° C.,75° C., 100° C., 125° C., 150° C., 175° C., or 200° C., and bounded atthe upper end by a value of about 450° C., 425° C., 400° C., 375° C.,350° C., 325° C., 300° C., 275° C., or 250° C. appear to be preferred.One exemplary, non-limiting, boiling point range, then, is from about80° C. to about 350° C. Exemplary, non-limiting solvents includebenzene, toluene, xylene, mesitylene, naphthalene, methyl cyclohexane,and dioxane.

As will be described further below, these chemical reducing systems arecapable of reductively cleaving C—O, C—N, or C—S bonds. It certainembodiments, these are alkyl C—O, C—N, or C—S bonds or aromatic C—O,C—N, or C—S bonds. In the context of alkyl or aromatic C—O, C—N, or C—Sbonds, the terms “alkyl” and “aromatic” refer to the nature of thecarbon to which the oxygen, nitrogen, or sulfur atoms are bonded. Asused herein, the general term “aromatic” refers to the ring moietieswhich satisfy the Hückel 4n+2 rule for aromaticity, and includes botharyl (i.e., carbocyclic) and heteroaryl structures, including aryl,aralkyl, alkaryl, heteroaryl, heteroaralkyl, or alk-heteroaryl moieties.Further, aromatic C—O, C—N, or C—S bonds can be configured to beendocyclic within the ring system (e.g., pyridine, furan, pyrrole, orthiophene) or exocyclic to the aromatic ring structure (e.g., as inanisole).

To this point, the invention has been described in terms of the chemicalsystems capable of reducing C—O, C—N, C—S bonds, or silylating aromaticcompounds or moieties, or a combination thereof, but it should also beapparent that the invention also includes the methods of carrying outthese transformations.

Methods for Reducing C—O, C—N, C—S Bonds

That is, various additional embodiments include those methods where anorganic substrate comprising C—O, C—N, C—S bonds, or a combinationthereof, are contacted with any of the chemical systems described aboveunder conditions sufficient to reduce at least a portion of these bonds.That is, certain embodiments provide methods of reducing C—X bonds in anorganic substrate, where X is O, N, or S, said method comprisingcontacting a quantity of the substrate comprising at least one C—O, C—N,or C—S bond with a chemical system comprising a mixture of (a) at leastone organosilane and (b) at least one strong base, under conditionssufficient to reduce the C—X bonds of at least a portion of the quantityof the substrate; wherein said chemical system is preferablysubstantially free of a transition-metal compound, and said chemicalsystem optionally comprising at least one molecular hydrogen donorcompound, molecular hydrogen, or both. In this context, the terms“reducing” and “reductive cleavage” carry the same definition asdescribed above; i.e., comprising chemical transformations wherein atleast some portion of the O, N, or S moieties are replaced by lesselectronegative groups, for example and including H, D, or Si. Thespecific nature of these chemical transformations is described herein.

In either case, in the context of the methods, the term “substantiallyfree of a transition-metal compound” carries the same connotations andrelated embodiments as described supra for the chemical system; i.e.,reflecting that the methods are effectively conducted in the absence ofany deliberately added transition-metal catalyst(s). Unless otherwisestated, when describing a method or system, the term is defined toreflect that the total level of transition metal, as measured by ICP-MSas described in Example 2 below, is less than about 50 ppm. Additionalembodiments also provide that the concentration of transition metals isless than about 100 ppm, 50 ppm, 30 ppm, 25 ppm, 20 ppm, 15 ppm, 10 ppm,or 5 ppm to about 1 ppm or 0 ppm. As used herein, the term “transitionmetal” is defined to mean Co, Rh, Ir, Fe, Ru, Os, Ni, Pd, Pt, Cu, orcombinations thereof. In further independent embodiments, theconcentration of Ni, as measured by ICP-MS, is less than 25 ppm, lessthan 10 ppm, less than 5 ppm, or less than 1 ppm. Noting here thatcertain embodiments of the chemical system may comprise the at least oneorganosilane, and strong base, and optionally further comprise at leastone molecular hydrogen donor, at least one substrate, additionalsolvent, or a combination thereof, it should be appreciated thatindependent embodiments provide that the levels of transition metals aremaintained below the levels just described, when considering each ofthese mixture combinations.

In the context of the cleavage methods, the term “substantially free ofwater and/or oxygen” carries the same connotations and relatedembodiments as described above for the system itself. Similarly, thesame organosilanes, strong bases, solvents, proportions, and operatingconditions described as useful for the system apply to the methods ofusing the systems. Additionally, as shown in the Examples, the systemhas shown to be useful when operated such that the organosilane and C—Xbonds in the substrate are present in a ratio of from about 1:2 to about10:1 and where the strong base and C—X bonds in the substrate arepresent in a range of from about 1:2 to about 10:1. A review of theresults shown in Example 5.9, Table 2 provides a helpful indicator as tothe effect of the ratios within these limits, and each ratio orcombination thereof represents an individual embodiment of thisinvention.

In those methods which have been described in terms of being conducted“under conditions sufficient to reduce the C—X bonds of at least aportion of the quantity of the substrate,” such conditions includeheating the contacted organic substrate and chemical system to atemperature in a range of from about 25° C. to about 450° C. Inindependent embodiments, this heating can be done at at least onetemperature in a range from about 25° C., about 50° C., about 75° C.,about 100° C., about 150° C., or about 200° C. to about 450° C., about400° C., about 350° C., about 300° C., about 250° C., about 200° C., orabout 150° C., including the temperatures exemplified herein. It ispreferred, but not required, that this heating is done in a solvent at atemperature below the boiling point of the solvent, and preferably, butnot necessarily, in a solvent at a temperature below the boiling pointof the solvent at one atmosphere pressure.

The term “to reduce the C—X bonds of at least a portion of the quantityof the substrate” refers to the condition where the cleavage of anindividual C—X bond proceeds to less than quantitative yield, to thecondition where the cleavage of an individual C—X bond proceeds toquantitative yield, to the condition where multiple C—X bonds exist inthe substrate (individual compound or mixture thereof) and only one typeof C—X bonds are cleaved, or a combination thereof. For purposes of thisdescription, unless otherwise stated, the reaction conditions areconsidered sufficient if at least 5% of at least one C—X bond (whereX═O, N, or S) is cleaved by the reaction. Higher yields are preferred,especially when dealing with individual compounds, so additionalindependent embodiments provide the reaction conditions are consideredsufficient if at least 10%, at least 20%, at least 30%, at least 40%, atleast 50%, at least 60%, at least 70%, at least 80%, at least 90%, or atleast 95% of at least one C—X bond is cleaved by the reaction. Inrelated embodiments, the method may produce a product in which at leastone of the C—X bonds is reduced by an amount ranging from a lower valueof about 10%, about 20%, about 30%, about 40%, about 50%, or about 60%and an upper value of about 100%, about 95%, about 90%, about 80%, about70%, about 60%, about 50%, or about 40%, relative to the amountoriginally present in the substrate compound.

Such high yields of any individual linkage may not be necessary wherethe substrate is an extended array of interconnected aromatics, such asfound in lignin (see, e.g., FIG. 1), coal, or petroleum products, inwhich case success may be measured by the reduction in molecular weightof the initial substrates.

The methods also cleave different C—X bonds to different efficiencies,under otherwise nomimally the same conditions. For example, as seen inExample 5.11, Schemes 1 and 2, aliphatic and aromatic C—O bonds behavedifferently, when contained within the same substrate. Further, whereasC—O and C—N bonds, by and large, produce products having residualalcohol or amine linkages, the same reaction conditions applied tosubstrates having C—S bonds generally result in products from which theS has been completely removed. Such desulfurization occurs even insubstrates which are historically difficult to desulfurize (e.g.,hindered dibenzothiophenes).

The methods appear to be operable on organic aromatic substrates,wherein the organic substrate comprises at least one C—O bond, at leastone C—N bond, at least one C—S bond, or a combination of such C—O, C—N,or C—S bonds. While the methods have been validated using a variety ofaromatic or heteroaromatic substrates, the C—O, C—N, or C—S bonds whichare cleaved are not necessarily aromatic C—O, C—N, or C—S bonds. In someembodiments, at least one of the C—O, C—N, or C—S bonds comprises anaromatic carbon. Within this set, the aromatic C—O, C—N, or C—S bondsmay be endocyclic or exocyclic to an aromatic ring. The terms“endocyclic” and “exocyclic” refer to the position of the O, N, or Swith respect to the aromatic ring system. For example, “endocyclic”refers to a bond in which both the carbon and the respective oxygen,nitrogen, or sulfur atoms are contained within the aromatic ring; furan,pyrrole, and thiophene contain endocyclic C—O, C—N, and C—S bonds,respectively. Accordingly, the organic substrate may comprise anoptionally substituted heteroaryl moiety which includes, but are notlimited to, a furan, pyrrole, thiophene, benzofuran, benzopyrrole,benzothiophene, 2,3-dihydrobenzofuran, xanthene,2,3-dihydrobenzopyrrole, 2,3-dihydrobenzothiophene, dibenzofuran,dibenzopyrol, dibenzothiophene, or hindered dibenzofuran,dibenzopyrrole, or dibenzothiophene structure. The term “hindereddibenzofuran, dibenzopyrrole, or dibenzothiophene structure” refers tothe presence of optionally substituted aryl, alkyl, or alkoxysubstituents in the 2,6 positions of the dibenzofuran, dibenzopyrrole,or dibenzothiophene. 2,6-Dimethyl dibenzothiophene is one importantexample of a hindered dibenzothiophene.

By contrast, the term “exocyclic” refers to a bond in which both thecarbon is contained within the aromatic rings system, but the respectiveoxygen, nitrogen, or sulfur atoms are not, and (in the case of nitrogen)vice versa. For example, phenol, phenylamine (aniline),1-methyl-1H-pyrrole, and benzenethiol contain exocyclic aromatic C—O,C—N, and C—S bonds, respectively. Exemplary organic substrates comprise,but are not limited to, optionally substituted phenyl ethers, phenylamines, phenyl sulfides, naphthyl ethers, naphthyl amines, or naphthylsulfides moiety, N-alkyl or N-aryl pyrroles, or combinations thereof.

As stated above, the methods are also operable on organic aromaticsubstrates, wherein the C—O, C—N, or C—S bonds which are cleaved arealiphatic (alkyl)C—O, C—N, or C—S bonds. Typically, but not necessarily,the aliphatic (alkyl)C—O, C—N, or C—S bonds are those in which theheteroatom is also joined by an aromatic C—O, C—N, or C—S bond—anisole(Ph-O—CH₃) and 1-methyl-1H-pyrrole are but two examples. Interestingly,and for reasons not entirely understood, the effect of the aromaticmoiety on bond cleavage has also been observed to extend beyond itsneighboring effect on the heteroatom. For example, in two examples:

Additional embodiments provide that these methods may be applied toorganic substrates batchwise or in a flowing stream, eitherindividually, or as part of a mixture. Indeed, it is particularlyattractive to apply these methods where the organic substrate iscontained within a petroleum, coal, natural gas, biomass (e.g, lignin,sugar), biopyrolysis oil, biomass liquifaction, or black liquor batch orprocess stream, or where such batch or process stream provides thesolvent for the reaction.

It is recognized that the systems and reactions which provide for thecleavage of the cleavage of the C—O, C—N, C—S bonds can also providesilylation of the aromatic substrates or even the aromatic solvents.This latter silylation feature is the subject of a co-filed andco-pending U.S. patent application Ser. No. 14/043,929, filed Oct. 2,2013, entitled “Transition-Metal-Free C—H Silylation of AromaticCompounds”, now U.S. Pat. No. 9,000,167, which issued Apr. 7, 2015,which is also incorporated by reference in its entirety for allpurposes. As used herein, the term “silylating” refers to the forming ofcarbon-silicon bonds, in a position previously occupied by acarbon-hydrogen bond, generally a non-activated C—H bond. The ability toreplace directly a C—H bond with a C—Si bond, under the conditionsdescribed herein, is believed to be unprecedented. The mechanism bywhich the system and methods operate is not yet understood, for example,whether the silylation is an intermediate step or a co-product orby-product of the cleavage reactions, but it does appear that therelative contribution of each manifold can be manipulated by thereaction conditions. For example, other factors being similar or equal,it appears that higher temperatures and longer reaction times favor thecleavage of C—O, C—N, C—S bonds over the silylation reactions.Similarly, absence of hydrogen and hydrogen donor molecules and use ofsub-stoichiometric quantities of the strong base (relative to theorganosilane) appear to favor the the silylation reactions and disfavorthe C—X cleavages.

Methods for Silylating Aromatic Compounds or Moieties

Various additional embodiments include those methods where an organicsubstrate comprising an aromatic moiety is contacted with any of thechemical systems described above under conditions sufficient to silylateat least a portion of the substrate. That is, certain embodimentsprovide methods, each method comprising contacting an organic substratecomprising an aromatic moiety with a mixture of (a) at least oneorganosilane and (b) at least one strong base, under conditionssufficient to silylate the substrate; wherein said mixture and substrateare optionally substantially free of a transition-metal compound. Theseembodiments are generally done in the liquid phase, without UVirradiation or electric or plasma discharge conditions.

In some embodiments, the conditions sufficient to silylate the organicsubstrate comprise heating the substrate with a mixture of (a) the atleast one organosilane and (b) the at least one strong base at atemperature in a range of about 10° C. to about 165° C. In some cases,the temperatures may be applied in a range of from about 20° C., about30° C., about 40° C., about 50° C., about 60° C., or about 80° C. toabout 165° C., about 150° C., about 125° C., about 100° C., or to aboutabout 80° C. Any of the temperatures described in the Examples may beconsidered independent embodiments. Typical operating reaction times mayrange from about 2 hours, from about 4 hours, from about 6 hours, orfrom about 10 hours to about 28 days, to about 14 days, to about 7 days,to about 4 days, to about 3 days, to about 48 hours, to about 24 hours,to about 12 hours, or to about 6 hours.

As described elsewhere herein, those features described as relevant forthe chemical systems for silylating aromatic compounds and aromaticmoieties are also relevant for the methods of silylating these aromaticcompounds and aromatic moieties. For example, in various embodiments,the methods provide that the system is substantially free of water,oxygen, or both water and oxygen, where these terms are describedelsewhere herein.

In related embodiments, at least one organosilane comprises anorganosilane of Formula (I) or Formula (II):(R)_(4-m)Si(H)_(m)(I)R—[—SiH(R)—O—]_(n)—R  (II)where m is 1, 2, or 3 (preferably 1);

n is 10 to 100; and

each R is independently optionally substituted C₁₋₁₂ alkyl orheteroalkyl, optionally substituted C₅₋₂₀ aryl or heteroaryl, optionallysubstituted C₆₋₃₀ alkaryl or heteroalkaryl, optionally substituted C₆₋₃₀aralkyl or heteroaralkyl, optionally substituted —O—C₁₋₁₂ alkyl orheteroalkyl, optionally substituted —O—C₅₋₂₀ aryl or heteroaryl,optionally substituted —O—C₆₋₃₀ alkaryl or heteroalkaryl, or optionallysubstituted —O—C₆₋₃₀ aralkyl or heteroaralkyl, and, if substituted, thesubstituents may be phosphonato, phosphoryl, phosphanyl, phosphino,sulfonato, C₁-C₂₀ alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀alkylsulfonyl, C₅-C₂₀ arylsulfonyl, C₁-C₂₀ alkylsulfinyl, C₅-C₂₀arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso,hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl, C₁-C₂₀thioester, cyano, cyanato, thiocyanato, isocyanate, thioisocyanate,carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl,boronato, boryl, or halogen, or a metal-containing ormetalloid-containing group, where the metalloid is Sn or Ge, where thesubstituents may optionally provide a tether to an insoluble orsparingly soluble support media comprising alumina, silica, or carbon.

In still other embodiments, the organosilane is (R)₃SiH, where R isindependently C₁₋₆ alkyl, preferably Et₃SiH or Et₂MeSiH. The at leastone strong base may comprise an alkali or alkaline earth metal hydride,as described above, for example, potassium hydride. The at least onestrong base may comprise an alkali or alkaline earth metal alkoxide, asdescribed above, for example, where the at least one alkoxide comprisesa C₁₋₁₂ linear or branched alkyl moiety or a C₅₋₁₀ aryl or heteroarylmoiety, preferably methoxide, ethoxide, propoxide, butoxide, or2-ethyl-hexyl alkoxide. The alkali metal cation is preferably potassiumor cesium. In most preferred embodiments, the organosilane istriethylsilane, trimethyl silane, diethylmethylsilane, diethylsilane,dimethylsilane, dimethylethylsilane, ethyldimethylsilane,dimethylphenylsilane, diethylphenylsilane and the strong base ispotassium tert-butoxide. Other combinations or exemplified reactantsprovide additional embodiments in this regard.

In certain embodiments, the organosilane (or monomer equivalent) and theat least one strong base are present together at a molar ratio, withrespect to one another, in a range of from about 20:1 to about 1:1. Incertain embodiments the at least one strong base and organic substrateare present together at a molar ratio, with respect to one another, in arange of from about 0.01:1 to about 5:1 But preferably the base issub-stoichiometric—i.e., in a ratio of 0.01:1 to 0.9:1—with respect tothe organic substrate. That is, the methods may be considered to becatalytic with respect to the strong base.

Additionally, in the context of the silylation methods, the term“substantially free of a transition-metal compound” carries the sameconnotations and related embodiments as described supra for the chemicalsystem; i.e., reflecting that the methods are effectively conducted inthe absence of any deliberately added transition-metal catalyst(s).Unless otherwise stated, when describing a method or system, the term isdefined to reflect that the total level of transition metal, as measuredby ICP-MS as described in Example 2 below, is less than about 50 ppm.Additional embodiments also provide that the concentration of transitionmetals is less than about 100 ppm, 50 ppm, 30 ppm, 25 ppm, 20 ppm, 15ppm, 10 ppm, or 5 ppm to about 1 ppm or 0 ppm, relative to the weight ofthe total system (i.e., both respect to the silylation system and thesilylation system and the organic substrate). As used herein, the term“transition metal” is defined to mean Co, Rh, Ir, Fe, Ru, Os, Ni, Pd,Pt, Cu, or combinations thereof. In further independent embodiments, theconcentration of Ni, as measured by ICP-MS, is less than 25 ppm, lessthan 10 ppm, less than 5 ppm, or less than 1 ppm. Noting here thatcertain embodiments of the chemical system may comprise the at least oneorganosilane, and strong base, it should be appreciated that independentembodiments provide that the levels of transition metals are maintainedbelow the levels just described, when considering each of these mixturecombinations.

Further embodiments provide that the methods further comprise usingsub-stoichiometric amounts (relative to the substrate) of N-basedcompounds including (preferably N-based chelants), for example,optionally substituted tetraalkylethylenediamine (e.g.,tetramethylethylenediamine), optionally substituted 1,7-phenanthrolinederivatives, optionally substituted 1,10-phenanthroline derivatives,optionally substituted 2,2′-bipyridine derivatives, and optionallysubstituted 4-dimethylaminopyridine derivatives.

The methods are fairly flexible with respect to substrates, andaccommodate both those containing both aryl and heteroaryl moieties.Exemplary substrates comprising aryl moieties include those comprisingoptionally substituted benzene (including mesitylene and toluene),biphenyl, naphthalene, anthracene, or higher polyaromatic ringstructures. These pure hydrocarbon substrates generally require moreforcing conditions to silylate the ring carbons than do heteroarylsystems. See Example 6.1. Nevertheless, the ability to functionalizethese hydrocarbon ring structures is an important feature of thesemethods and systems.

Where the aryl or heteroaryl moiety comprises an alpha-methyl ormethylene C—H bond, as in an optionally substituted C₁₋₆ alkyl group (asexemplified by methyl groups of toluene, mesitylene, 1,2 dimethylindole,or 2,5-dimethylthiophene in the Examples), it appears that the reactionproceeds to form alpha silanes at temperatures lowered than required tosilylate the ring carbons. As used herein, the term “alpha carbon”refers to the first carbon positioned exocyclic to the aromatic moeity,and “alpha” as in “alpha methyl or methylene” is intended to refer tothe methyl or methylene on the first exocyckic carbon directly attachedto the aromatic ring. The term “alpha silane” refers a silane bonded tothe alpha carbon. The term “alpha” is considered to encompass benzyliccarbons for 6 membered aryl aromatics. Methods resulting in suchsilylations are within the scope of the present invention.

Other exocyclic ring substituents, including those having an exocyclicaromatic C—X bond, generally react according to the methods describedherein. The term “exocyclic” refers to the position of the O, N, or Swith respect to the aromatic ring system. For example, the term“exocyclic” refers to a bond in which the carbon is contained within thearomatic rings system, but the respective oxygen, nitrogen, or sulfuratoms are not and, (in the case of nitrogen), vice versa. For example,phenol, dimethylaniline, 1-methyl-1H-pyrrole, and benzenethiol containexocyclic aromatic C—O, C—N, and C—S bonds, respectively. Exemplaryorganic substrates comprise, but are not limited to, optionallysubstituted phenyl ethers, phenyl amines, phenyl sulfides, naphthylethers, naphthyl amines, or naphthyl sulfides moiety, N-alkyl or N-arylpyrroles, or combinations thereof.

Where X is O or N, the reaction favors silylation of the ring ortho orat the carbon adjacent to the carbon containing the exocyclic C—X bond.Electron-rich systems or electron-donating groups or substituents appearto be generally more reactive than electron-poor systems orelectron-withdrawing groups or substituents; the latter may require moreforcing conditions than the former, but note that more forcingconditions derived from higher temperatures may result in driving theC—X cleavage manifold. Anisole and 2-methoxynaphthalene show aparticular preference to the ortho position, and this selectivityprovides the basis for embodiments comprising the selective orthosilylation of such substrates. See, e.g., Examples 6.2.1 and 6.2.2.Interesting, and by contrast, those substrates having an exocyclicaromatic C—X bond, where X is S-alkyl provides a different reactivity,showing a proclivity to silylate the alkyl group rather than thearomatic ring system. See, e.g., Example 6.2.4. This reactivity patternprovides a basis for those embodiments comprising the β-silylation ofsuch substrates.

In certain embodiments, the methods are applied to an organic substratecomprising a heteroaryl moiety. Non-limiting heteroaryl moieties includethose comprising an optionally substituted furan, pyrrole, thiophene,pyrazole, imidazole, triazole, isoxazole, oxazole, thiazole,isothiazole, oxadiazole, pyridine, pyridazine, pyrimidine, pyrazine,triazone, benzofuran, benzopyrrole, benzothiophene, isobenzofuran,isobenzopyrrole, isobenzothiophene, indole, isoindole, indolizine,indazole, azaindole, benzisoxazole, benzoxazole, quinoline,isoquinoline, cinnoline, quinazoline, naphthyridine,2,3-dihydrobenzofuran, 2,3-dihydrobenzopyrrole,2,3-dihydrobenzothiophene, dibenzofuran, xanthene, dibenzopyrol,dibenzothiophene. In more preferred embodiments, the substrate comprisesa moiety comprising an optionally substituted furan, pyrrole, thiophene,pyrazole, imidazole, benzofuran, benzopyrrole, benzothiophene, indole,azaindole dibenzofuran, xanthene, dibenzopyrrole, or dibenzothiophenemoiety. Independent embodiments provide that the methods yield silylatedproducts substituted as described herein.

In other specific embodiments, the methods are operable on substratescomprising the following moieties:

where X is N—R″, O, or S;

Y is H, N(R″)₂, O—R″, or S—R″

p is 0 to 4, 0 to 3, 0 to 2, or 0 to 1;

R′ is a functional group “Fn,” as described above, or (R′)_(p) is afused alicyclic, heteroalicyclic, aryl or heteroaryl moiety; and

R″ is an amine protecting group or an optionally substituted alkyl,aryl, heteroaryl, alkaryl or alk-heteroaryl, preferably optionallysubstituted C₁-C₆ alkyl, phenyl, tolyl, benzyl, or phenethyl.

In certain more specific embodiments, the methods are operable onorganic substrates comprising the following moieties:

where X, Y, R′, R″ and p are as defined above. Note that the designation

in each case, is intended to allow for substitution on either aromaticring.

Heteroaryl moieties appear to react according to the inventive methodsunder conditions that are milder than their aryl cogeners, such that, inmixed aryl-heteroaryl systems, reactions generally proceed to silylatethe heteroaryl ring preferentially. For example, as shown in Examples6.3.1 to 6.4.7 and 6.4.11 to 6.3.13, silylation is shown to occurpreferentially in the heterocylic portion of the molecule. However, andas shown in Example 6.3.10, where an aryl moiety is proximatelypositioned to a (presumed first) silylated heteroaryl, the silylation ofthat aryl moiety occurs at much milder conditions than those requiredfor the aryl-only system (cf. Examples 6.2.3 and 6.3.10). This abilityto form silylated ring structures from heteroaryl precursors, is anotheruseful feature and embodiment of the present inventions.

Also, 5-membered heteroaryl moieties appear to react according to theinventive methods under conditions that are milder than even 6-memberedheteroaryl moieties. For example, as shown in Example 6.3.6,N-methyazalindole is shown to silylate preferentially in the 5-memberedheterocylic portion of the molecule. And both rings silylate underconditions much milder than found for pyridine.

The silylation reactions with substrates comprising 5-memberedheteroaryl moieities also provide remarkably clean and apparentlytunable regioselectivities. Substrates comprising 5-membered heteroarylrings containing at least N can silylate at the C-2 or C-3 position,depending on time and temperature. While not intending to be bound bythe correctness or incorrectness of any particular theory, it appearsthat silylation at the C-2 position may represent the kinetic result ofthe reaction, whereas silylation at the C-3 position may bethermodynamically favored. While described in terms of “kinetic” and“thermodynamic” pathways, it is not clear that silylation at a C-3position necessarily proceeds through a C-2 intermediate. Indeed,experiments using 1,2 dimethyl indole and 2,5-dimethyl thiophene, wherethe C-2 positions are blocked by methyl groups, reaction proceeded tosilylate the alpha-methyl group preferentially, with no evidence forsilylation in the C-3 position.

Unless otherwise stated, reference to silylation at a specific positionis intended to connote a regioselectivity or regiospecificity of aproduct at that position of greater than about 80%. But otherembodiments provide that the regiospecificity at that position isgreater than about 50%, greater than about 75%, greater than about 90%,or greater than about 95%.

The products of the inventive methods are useful in a range ofagrichemical, pharmaceutical, and electronics applications, as describedinfra. They also provide useful intermediates for subsequent syntheses.The use of aromatic silanes, such as those described herein, are usefulsynthons for the preparation of biaryl/biaromatic compounds, forexample, using the Hiyama coupling methods generally recognized in theart. The skilled artisan would be well able to combine the teachings ofthese Hiyama coupling methods with those presented here, without undueexperimentation, to prepare biaryl/biaromatic compounds, and suchpreparations are considered within the scope of the present invention.Also, Ball and colleagues (Ball et al., Science 28 Sep. 2012: Vol. 337no. 6102 pp. 1644-1648, which is incorporated by reference herein forits teaching of the catalysts, methods, and substrates) have morerecently described another method, using gold catalysts, to coupletrialkyl silanes, such as those described herein, to formbiaryl/biaromatic compounds. Again, the skilled artisan would be wellable to combine the teachings of the Ball coupling, including at leastthe second aryl compounds taught or suggested in the Ball reference,again without undue experimentation, to prepare biaryl compounds, andsuch methods and preparations are considered within the scope of thepresent invention. In such embodiments, a silylated product of thepresent invention, whether isolated or generated in situ, is furtherreacted under conditions (including the presence of a suitabletransition metal catalyst) sufficient to couple the silylated productwith a second aromatic compound to prepare the biaryl product. Asintended herein, the second aromatic compound comprises an optionallysubstituted aromatic moiety, including optionally substituted aryl andheteroarly moieties, where the terms “optionally substituted,”“aromatic,” “aryl,” and “heteroaryl” carry the same definitions asalready described herein.

The conversion of aromatic silanes, such as those described herein, arealso known to be convertible to aromatic hydroxy compounds, using thewell-known Fleming-Tamao oxidation methods. The skilled artisan would bewell able to combine the teachings of these Fleming-Tamao oxidationswith those presented here, again without undue experimentation, toprepare hydroxylated aromatic compounds, and such methods andpreparations are considered within the scope of the present invention.In such embodiments, the aromatic silylated products of the presentinvention, whether isolated or generated in situ, are further reactedunder conditions (including the presence of a suitable transition metalcatalyst) sufficient to convert the silylated product to hydroxylatedaromatic products.

Also, the ability of the present invention to silylate alpha-carbonsubstituents (or β-silyl groups in the case of exocyclic sulfur) alsoprovides that those products may be used as synthons for the Petersonolefination reaction. The known ease of deprotonating thealpha-methylene proton, when adjacent to the silane silicon (the “alphasilicon effect”) to yield an alpha-silyl carbanion can form a convenientprecursor for this olefination reaction. The skilled artisan would bewell able to combine the teachings of these Peterson olefinationreaction with those presented here, again without undue experimentation,to replace the alpha silyl groups with alpha olefins, and such methodsand preparations are considered within the scope of the presentinvention. In such embodiments, the aromatic silylated products of thepresent invention, whether isolated or generated in situ, are furtherreacted under conditions sufficient (including the presence of asuitable transition metal catalyst) to convert the silylated product toaromatic alpha-olefin products.

The following listing of embodiments in intended to complement, ratherthan displace or supersede, the previous descriptions.

Embodiment 1

A chemical system for reducing C—O, C—N, and C—S bonds, said systemcomprising a mixture of (a) at least one organosilane and (b) at leastone strong base, said system preferably being substantially free of atransition-metal compound, and said system optionally comprising atleast one molecular hydrogen donor compound, molecular hydrogen, orboth.

Embodiment 2

The system of Embodiment 1, further comprising at least one molecularhydrogen donor compound, hydrogen, or both.

Embodiment 3

The system of Embodiment 1 or 2, that is capable of reductively cleavingC—O, C—N, or C—S bonds.

Embodiment 4

The system of any one of Embodiments 1 to 3, that is capable ofreductively cleaving aromatic C—O, C—N, or C—S bonds.

Embodiment 5

The system of Embodiment 4, wherein the C—O, C—N, or C—S bonds areexocyclic to an aromatic ring moiety.

Embodiment 6

The system of Embodiment 4, wherein the C—O, C—N, or C—S bonds areendocyclic to an aromatic ring moiety.

Embodiment 7

The system of any one of Embodiments 1 to 3, that is capable ofreductively cleaving aliphatic C—O, C—N, or C—S bonds.

Embodiment 8

The system of any one of Embodiments 1 to 7, that is substantially freeof water, oxygen, or both water and oxygen.

Embodiment 9

The system of any one of Embodiments 1 to 8, wherein at least oneorganosilane comprises an organosilane of Formula (I) or Formula (II):(R)_(4-m)Si(H)_(m)  (I)R—[—SiH(R)—O—]_(n)—R  (II)where: m is 1, 2, or 3; n is 10 to 100; and R is independentlyoptionally substituted C₁₋₁₂ alkyl or heteroalkyl, C₅₋₂₀ aryl orheteroaryl, C₆₋₃₀ alkaryl or heteroalkaryl, C₆₋₃₀ aralkyl orheteroaralkyl, —O—C₁₋₁₂ alkyl or heteroalkyl, —O—C₅₋₂₀ aryl orheteroaryl, —O—C₆₋₃₀ alkaryl or heteroalkaryl, —O—C₆₋₃₀ aralkyl orheteroaralkyl, and, if substituted, the substituents may be phosphonato,phosphoryl, phosphanyl, phosphino, sulfonato, C₁-C₂₀ alkylsulfanyl,C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfonyl, C₅-C₂₀ arylsulfonyl, C₁-C₂₀alkylsulfinyl, C₅-C₂₀ arylsulfinyl, sulfonamido, amino, amido, imino,nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₂-C₂₀alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, carboxyl, carboxylato, mercapto,formyl, C₁-C₂₀ thioester, cyano, cyanato, thiocyanato, isocyanate,thioisocyanate, carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl,siloxazanyl, boronato, boryl, or halogen, or a metal-containing ormetalloid-containing group, where the metalloid is Sn or Ge, where thesubstituents may optionally provide a tether to an insoluble orsparingly soluble support media comprising alumina, silica, or carbon.

Embodiment 10

The system of Embodiment 9, wherein the organosilane is (R)₃SiH, where Ris C₁₋₆ alkyl.

Embodiment 11

The system of any one of Embodiments 1 to 10, wherein the at least onestrong base comprises an alkali or alkaline metal hydride or alkoxide.

Embodiment 12

The system of any one of Embodiments 1 to 11, wherein the at least onestrong base comprises an alkali or alkaline metal hydride.

Embodiment 13

The system of Embodiment 12, wherein the at least one strong basecomprises potassium hydride.

Embodiment 14

The system of any one of Embodiments 1 to 11, wherein the at least onestrong base comprises an alkali or alkaline metal alkoxide.

Embodiment 15

The system of Embodiment 14, wherein the at least one alkoxide comprisesa C₁₋₁₂ linear or branched alkyl moiety or a C₅₋₁₀ aromatic orheteroaromatic moiety.

Embodiment 16

The system of Embodiment 15, wherein the at least one alkoxide comprisesmethoxide, ethoxide, propoxide, butoxide, or 2-ethyl-hexyl alkoxide.

Embodiment 17

The system of any one of Embodiments 11 to 16, wherein the alkali oralkaline metal hydride or alkoxide base is a potassium or cesiumalkoxide.

Embodiment 18

The system of any one of Embodiments 1 to 17, where the organosilane istriethylsilane and the strong base is potassium t-butoxide.

Embodiment 19

The system of any one of Embodiments 1 to 18, wherein the organosilaneand the at least one strong base are present together at a molar ratio,with respect to one another, in a range of from about 20:1 to about 1:2.

Embodiment 20

The system of any one of Embodiments 1 to 19, further comprising anorganic compound, said compound being a solvent, a substrate, or both asolvent and a substrate.

Embodiment 21

The system of Embodiment 20, wherein the organic compound is an organicsolvent having a boiling point at one atmosphere pressure in a range offrom about 25° C. to about 450° C.

Embodiment 22

The system of Embodiment 20 or 21, wherein the organic compound is anorganic substrate containing oxygen, nitrogen, sulfur, or a combinationthereof.

Embodiment 23

The system of Embodiment 22, wherein the organic substrate is containedwithin a biomass (e.g, lignin, sugar), biomass liquifaction,biopyrolysis oil, black liquor, coal, coal liquifaction, natural gas, orpetroleum process stream.

Embodiment 24

The system of any one of Embodiments 1 to 23, wherein thetransition-metal compound is present at less than 10 ppm, relative tothe weight of the total system.

Embodiment 25

The system of any one of Embodiments 1 to 24, wherein the hydrogen donorcompound comprises 1,3-cyclohexadiene, 1,4-cyclohexadiene,1,2-cyclohexadiene, 1,4-cyclohexadiene 1,2-dihydronaphthalene,1,4-dihydronaphthalene, 1,2-dihydroquinoline, 3,4-dihydroquinoline,9,10-dihydroanthracene, or tetralin.

Embodiment 26

A method of reducing C—X bonds in a an organic substrate, where X is O,N, or S, said method comprising contacting a quantity of the substratecomprising at least one C—O, C—N, or C—S bond with a chemical systemcomprising a mixture of (a) at least one organosilane and (b) at leastone strong base, under conditions sufficient to reduce the C—X bonds ofat least a portion of the quantity of the substrate; wherein saidchemical system is preferably substantially free of a transition-metalcompound, and said chemical system optionally comprising at least onemolecular hydrogen donor compound, molecular hydrogen, or both.

Embodiment 27

The method of Embodiment 26, further comprising at least one molecularhydrogen donor compound, hydrogen, or both.

Embodiment 28

The method of Embodiment 26 or 27, wherein the organic substratecomprises at least one C—O bond, and optionally at least one C—N bond,C—S bond, or both C—N and C—S bonds.

Embodiment 29

The method of Embodiment 26 or 27, wherein the organic substratecomprises at least one C—N bond, and optionally at least one C—O bond,C—S bond, or both C—O and C—S bonds.

Embodiment 30

The method of Embodiment 26 or 27, wherein the organic substratecomprises at least one C—S bond, and optionally at least one C—O bond,C—N bond, or both C—O and C—N bonds.

Embodiment 31

The method of any one of Embodiments 26 to 30, further comprising atleast one molecular hydrogen donor compound, molecular hydrogen itself,or both.

Embodiment 32

The method of any one of Embodiments 26 to 31, wherein at least one ofthe C—O, C—N, or C—S bonds is an aromatic C—O, C—N, or C—S bond.

Embodiment 33

The method of Embodiment 32, wherein at least one of the C—O, C—N, orC—S bonds is exocyclic to an aromatic ring moiety.

Embodiment 34

The method of any one of Embodiments 33, wherein at least one of theC—O, C—N, or C—S bonds is endocyclic to an aromatic ring moiety.

Embodiment 35

The method of any one of Embodiments 26 to 34, wherein the substratecomprises an optionally substituted phenyl ether, phenyl amine, phenylsulfide, naphthyl ether, naphthyl amine, or naphthyl sulfide moiety, orcombination thereof.

Embodiment 36

The method of any one of Embodiments 26 to 35, wherein the substratecomprises a furan, pyrrole, thiophene, benzofuran, benzopyrrole,benzothiophene, 2,3-dihydrobenzofuran, 2,3-dihydrobenzopyrrole,2,3-dihydrobenzothiophene, dibenzofuran, xanthene, dibenzopyrol,dibenzothiophene, or hindered dibenzofuran, dibenzopyrrole, ordibenzothiophene moiety.

Embodiment 37

The method of any one of Embodiments 26 to 32 wherein at least one ofthe C—O, C—N, or C—S bonds is an aliphatic C—O, C—N, or C—S bond.

Embodiment 38

The method of any one of Embodiments 26 to 37, that is substantiallyfree of water, oxygen, or both water and oxygen.

Embodiment 39

The method of any one of Embodiments 26 to 38, wherein at least oneorganosilane comprises an organosilane of Formula (I) or Formula (II):(R)_(4-m)Si(H)_(m)(I)R—[—SiH(R)—O—]_(n)—R  (II)where m is 1, 2, or 3; n is 10 to 100; and R is independently optionallysubstituted C₁₋₁₂ alkyl or heteroalkyl, C₅₋₂₀ aryl or heteroaryl, C₆₋₃₀alkaryl or heteroalkaryl, C₆₋₃₀ aralkyl or heteroaralkyl, —O—C₁₋₁₂ alkylor heteroalkyl, —O—C₅₋₂₀ aryl or heteroaryl, —O—C₆₋₃₀ alkaryl orheteroalkaryl, —O—C₆₋₃₀ aralkyl or heteroaralkyl, and, if substitutedthe substituents may be phosphonato, phosphoryl, phosphanyl, phosphino,sulfonato, C₁-C₂₀ alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀alkylsulfonyl, C₅-C₂₀ arylsulfonyl, C₁-C₂₀ alkylsulfinyl, C₅-C₂₀arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso,hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl, C₁-C₂₀thioester, cyano, cyanato, thiocyanato, isocyanate, thioisocyanate,carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl,boronato, boryl, or halogen, or a metal-containing ormetalloid-containing group, where the metalloid is Sn or Ge, where thesubstituents may optionally provide a tether to an insoluble orsparingly soluble support media comprising alumina, silica, or carbon.

Embodiment 40

The method of Embodiment 39, wherein the organosilane is (R)₃SiH, whereR is C₁₋₆ alkyl.

Embodiment 41

The method of any one of Embodiments 26 to 40, wherein the at least onestrong base comprises an alkali or alkaline metal hydride or alkoxide.

Embodiment 42

The method of any one of Embodiments 26 to 41, wherein the at least onestrong base comprises an alkali or alkaline metal hydride.

Embodiment 43

The method of Embodiment 42, wherein the at least one strong basecomprises potassium hydride.

Embodiment 44

The method of any one of Embodiments 26 to 43, wherein the at least onestrong base comprises an alkali or alkaline metal alkoxide.

Embodiment 45

The method of Embodiment 44, wherein the at least one alkoxide comprisesa C₁₋₁₂ linear or branched alkyl moiety or a C₅₋₁₀ aromatic orheteroaromatic moiety.

Embodiment 46

The method of Embodiment 45, wherein the at least one alkoxide comprisesmethoxide, ethoxide, propoxide, butoxide, or 2-ethyl-hexyl alkoxide.

Embodiment 47

The method of any one of Embodiments 39 to 46, wherein the alkali oralkaline metal hydride or alkoxide base is a potassium or cesiumalkoxide.

Embodiment 48

The method of any one of Embodiments 26 to 47, where the organosilane istriethylsilane and the strong base is potassium t-butoxide.

Embodiment 49

The method of any one of Embodiments 26 to 48, wherein the organosilaneand the at least one strong base are present together at a molar ratio,with respect to one another, in a range of from about 20:1 to about 1:2.

Embodiment 50

The method of any one of Embodiments 26 to 49, wherein the organosilaneand C—X bonds in the substrate are present in a ratio of from about 1:2to about 10:1.

Embodiment 51

The method of any one of Embodiments 26 to 50, wherein the strong baseand C—X bonds in the substrate are present in a range of from about 1:2to about 10:1.

Embodiment 52

The method of any one of Embodiments 26 to 49, wherein the organosilaneis present in sufficient quantity to act as a solvent for the method.

Embodiment 53

The method of any one of Embodiments 26 to 51, further comprising anorganic solvent.

Embodiment 54

The method of Embodiment 53, said organic solvent having a boiling pointat one atmosphere pressure in a range of from about 25° C. to about 450°C.

Embodiment 55

The method of any one of Embodiments 26 to 54, said method comprisingheating the organic substrate and chemical system to a temperature in arange of from about 25° C. to about 450° C.

Embodiment 56

The method of any one of Embodiments 26 to 55, wherein thetransition-metal compound is present at less than 10 ppm, relative tothe weight of the total system.

Embodiment 57

The method of any one of Embodiments 26 to 56, wherein the hydrogendonor compound comprises 1,3-cyclohexadiene, 1,4-cyclohexadiene,1,2-cyclohexadiene, 1,4-cyclohexadiene 1,2-dihydronaphthalene,1,4-dihydronaphthalene, 1,2-dihydroquinoline, 3,4-dihydroquinoline,9,10-dihydroanthracene, or tetralin.

Embodiment 58

The method of any one of Embodiments 26 to 57, wherein the organicsubstrate is contained within a biomass (e.g, lignin, sugar), biomassliquifaction, biopyrolysis oil, black liquor, coal, coal liquifaction,natural gas, or petroleum process stream.

Embodiment 59

The method of any one of Embodiments 26 to 58, wherein said method isconducted within a biomass (e.g, lignin, sugar), biomass liquifaction,biopyrolysis oil, black liquor, coal, coal liquifaction, natural gas, orpetroleum process stream.

Embodiment 60

The method of any one of Embodiments 26 to 59, wherein the methodproduces a product in which at least one of the C—X bonds are reduced inan amount ranging from about 40% to 100%, relative to the amountoriginally present in the substrate compound.

Embodiment 61

A chemical system for silylating an organic substrate comprising anaromatic moiety, said system comprising a mixture of (a) at least oneorganosilane and (b) at least one strong base, said system preferablybeing substantially free of transition-metal compounds.

Embodiment 62

The system of Embodiment 61, wherein the transition-metal compound ispresent at less than 10 ppm, relative to the weight of the total system.

Embodiment 63

The chemical system of Embodiment 61 or 62, further comprising anoptionally substituted tetraalkylethylenediamine (e.g.,tetramethylethylenediamine), an optionally substituted1,7-phenanthroline derivative, an optionally substituted1,10-phenanthroline derivative, an optionally substituted2,2′-bipyridine derivatives, or an optionally substituted4-dimethylaminopyridine derivative.

Embodiment 64

The system of any one of Embodiments 61 to 63, that is substantiallyfree of water, oxygen, or both water and oxygen.

Embodiment 65

The system of any one of Embodiments 61 to 64, wherein at least oneorganosilane comprises an organosilane of Formula (I) or Formula (II):(R)_(4-m)Si(H)_(m)  (I)R—[—SiH(R)—O—]_(n)—R  (II)where: m is 1, 2, or 3; n is 10 to 100; and each R is independentlyoptionally substituted C₁₋₁₂ alkyl or heteroalkyl, optionallysubstituted C₅₋₂₀ aryl or heteroaryl, optionally substituted C₆₋₃₀alkaryl or heteroalkaryl, optionally substituted C₆₋₃₀ aralkyl orheteroaralkyl, optionally substituted —O—C₁₋₁₂ alkyl or heteroalkyl,optionally substituted —O—C₅₋₂₀ aryl or heteroaryl, optionallysubstituted —O—C₆₋₃₀ alkaryl or heteroalkaryl, or optionally substituted—O—C₆₋₃₀ aralkyl or heteroaralkyl, and, if substituted, the substituentsmay be phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C₁-C₂₀alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀ alkylsulfonyl, C₅-C₂₀arylsulfonyl, C₁-C₂₀ alkylsulfinyl, C₅-C₂₀ arylsulfinyl, sulfonamido,amino, amido, imino, nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀aryloxy, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀ aryloxycarbonyl, carboxyl,carboxylato, mercapto, formyl, C₁-C₂₀ thioester, cyano, cyanato,thiocyanato, isocyanate, thioisocyanate, carbamoyl, epoxy, styrenyl,silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, or halogen, or ametal-containing or metalloid-containing group, where the metalloid isSn or Ge, where the substituents may optionally provide a tether to aninsoluble or sparingly soluble support media comprising alumina, silica,or carbon.

Embodiment 66

The system of Embodiment 65, wherein the organosilane is (R)₃SiH, whereR is C₁₋₆ alkyl.

Embodiment 67

The system of any one of Embodiments 61 to 66, wherein the at least onestrong base comprises an alkali or alkaline earth metal hydride oralkoxide.

Embodiment 68

The system of any one of Embodiments 61 to 67, wherein the at least onestrong base comprises an alkali or alkaline earth metal hydride.

Embodiment 69

The system of Embodiment 68, wherein the at least one strong basecomprises potassium hydride.

Embodiment 70

The system of any one of Embodiments 61 to 67, wherein the at least onestrong base comprises an alkali or alkaline earth metal alkoxide.

Embodiment 71

The system of Embodiment 70, wherein the at least one alkoxide comprisesa C₁₋₁₂ linear or branched alkyl moiety or a C₅₋₁₀ aromatic orheteroaromatic moiety.

Embodiment 72

The system of Embodiment 71, wherein the at least one alkoxide comprisesmethoxide, ethoxide, propoxide, butoxide, or 2-ethyl-hexyl alkoxide.

Embodiment 73

The system of any one of Embodiments 67 to 72, wherein the alkali oralkaline earth metal hydride or alkoxide base is a potassium or cesiumalkoxide.

Embodiment 74

The system of any one of Embodiments 61 to 73, where the organosilane istriethylsilane and the strong base is potassium tert-butoxide.

Embodiment 75

The system of any one of Embodiments 61 to 74, wherein the organosilaneand the at least one strong base are present together at a molar ratio,with respect to one another, in a range of from about 20:1 to about 1:1.

Embodiment 76

The system of any one of Embodiments 61 to 75, further comprising anorganic aromatic compound, said compound being a solvent, a substrate,or both a solvent and a substrate.

Embodiment 77

The system of Embodiment 76, wherein the organic compound comprises anoptionally substituted benzene, biphenyl, naphthalene, or anthracenering structure.

Embodiment 78

The system of Embodiment 76 or 77, wherein the organic aromatic compoundcomprises a heteroaryl moiety.

Embodiment 79

The system of Embodiment 78, wherein the organic aromatic compoundcomprises an optionally substituted furan, pyrrole, thiophene, pyrazole,imidazole, triazole, isoxazole, oxazole, thiazole, isothiazole,oxadiazole, pyridine, pyridazine, pyrimidine, pyrazine, triazone,benzofuran, benzopyrrole, benzothiophene, isobenzofuran,isobenzopyrrole, isobenzothiophene, indole, isoindole, indolizine,indazole, azaindole, benzisoxazole, benzoxazole, quinoline,isoquinoline, cinnoline, quinazoline, naphthyridine,2,3-dihydrobenzofuran, 2,3-dihydrobenzopyrrole,2,3-dihydrobenzothiophene, dibenzofuran, xanthene, dibenzopyrol, ordibenzothiophene moiety.

Embodiment 80

The system of Embodiment 78 or 79, wherein the organic aromatic compoundcomprises an optionally substituted furan, pyrrole, thiophene, pyrazole,imidazole, benzofuran, benzopyrrole, benzothiophene, indole, azaindole,dibenzofuran, xanthene, dibenzopyrrole, dibenzothiophene, or a hindereddibenzofuran, dibenzopyrrole, or dibenzothiophene moiety.

Embodiment 81

The system of any one of Embodiments 76 to 80, wherein the organicaromatic compound comprises at least one of the following moieties:

where X is N—R″, O, or S;

Y is H, N(R″)₂, O—R″, or S—R″

p is 0 to 4, 0 to 3, 0 to 2, or 0 to 1;

R′ is a functional group “Fn,” as described above, or (R′)_(p) is anoptionally substituted fused alicyclic, heteroalicyclic, aryl orheteroaryl moiety; and

R″ is an amine protecting group or an optionally substituted alkyl,aryl, heteroaryl, alkaryl or alk-heteroaryl, preferably optionallysubstituted C₁-C₆ alkyl, phenyl, tolyl, benzyl, or phenethyl.

Embodiment 82

The system of any one of Embodiments 76 to 81, wherein the substratecomprises at least one of the following moieties:

where X, Y, R′, R″ and p are as defined above. Note that the designation

in each case, is intended to allow for substitution on either aromaticring.

Embodiment 83

The system of method of any one of Embodiments 76 to 81, wherein thearomatic organic compound comprises at least one alpha-methyl ormethylene C—H bond, said method resulting in the formation of an alphasilane.

Embodiment 84

A method of silylating a substrate comprising an aromatic moiety, saidmethod comprising contacting a quantity of the organic substrate with asystem of any one of Embodiments 1 to 83.

Embodiment 85

A method comprising contacting an organic substrate comprising anaromatic moiety with a mixture of (a) at least one organosilane and (b)at least one strong base, under conditions sufficient to silylate thesubstrate; wherein said mixture and substrate are preferablysubstantially free of transition-metal compounds.

Embodiment 86

The method of Embodiment 85, wherein the transition-metal compound ispresent at less than 10 ppm, relative to the weight of the total system.

Embodiment 87

The method of Embodiments 85 or 86, wherein the mixture furthercomprises an optionally substituted tetraalkylethylenediamine (e.g.,tetramethylethylenediamine), an optionally substituted1,7-phenanthroline derivative, an optionally substituted1,10-phenanthroline derivative, an optionally substituted2,2′-bipyridine derivatives, or an optionally substituted4-dimethylaminopyridine derivative.

Embodiment 88

The method of any one of Embodiments 85 to 27, that is substantiallyfree of water, oxygen, or both water and oxygen.

Embodiment 29

The method of any one of Embodiments 85 to 88, wherein at least oneorganosilane comprises an organosilane of Formula (I) or Formula (II):(R)_(4-m)Si(H)_(m)(I)R—[—SiH(R)—O—]_(n)—R  (II)where m is 1, 2, or 3 (preferably 1);

n is 10 to 100; and

and each R is independently optionally substituted C₁₋₁₂ alkyl orheteroalkyl, optionally substituted C₅₋₂₀ aryl or heteroaryl, optionallysubstituted C₆₋₃₀ alkaryl or heteroalkaryl, optionally substituted C₆₋₃₀aralkyl or heteroaralkyl, optionally substituted —O—C₁₋₁₂ alkyl orheteroalkyl, optionally substituted —O—C₅₋₂₀ aryl or heteroaryl,optionally substituted —O—C₆₋₃₀ alkaryl or heteroalkaryl, or optionallysubstituted —O—C₆₋₃₀ aralkyl or heteroaralkyl, and, if substituted, thesubstituents may be phosphonato, phosphoryl, phosphanyl, phosphino,sulfonato, C₁-C₂₀ alkylsulfanyl, C₅-C₂₀ arylsulfanyl, C₁-C₂₀alkylsulfonyl, C₅-C₂₀ arylsulfonyl, C₁-C₂₀ alkylsulfinyl, C₅-C₂₀arylsulfinyl, sulfonamido, amino, amido, imino, nitro, nitroso,hydroxyl, C₁-C₂₀ alkoxy, C₅-C₂₀ aryloxy, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₀aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl, C₁-C₂₀thioester, cyano, cyanato, thiocyanato, isocyanate, thioisocyanate,carbamoyl, epoxy, styrenyl, silyl, silyloxy, silanyl, siloxazanyl,boronato, boryl, or halogen, or a metal-containing ormetalloid-containing group, where the metalloid is Sn or Ge, where thesubstituents may optionally provide a tether to an insoluble orsparingly soluble support media comprising alumina, silica, or carbon.

Embodiment 90

The method of any one of Embodiments 85 to 89, wherein the organosilaneis (R)₃SiH, where R is independently C₁₋₆ alkyl.

Embodiment 91

The method of any one of Embodiments 25 to 90, wherein the at least onestrong base comprises an alkali or alkaline earth metal hydride oralkoxide.

Embodiment 92

The method of any one of Embodiments 85 to 91, wherein the at least onestrong base comprises an alkali or alkaline earth metal hydride.

Embodiment 93

The method of Embodiment 32, wherein the at least one strong basecomprises potassium hydride.

Embodiment 34

The method of any one of Embodiments 85 to 93, wherein the at least onestrong base comprises an alkali or alkaline earth metal alkoxide.

Embodiment 95

The method of Embodiment 94, wherein the at least one alkoxide comprisesa C₁₋₁₂ linear or branched alkyl moiety or a C₅₋₁₀ aryl or heteroarylmoiety.

Embodiment 96

The method of Embodiment 95, wherein the at least one alkoxide comprisesmethoxide, ethoxide, propoxide, butoxide, or 2-ethyl-hexyl alkoxide.

Embodiment 97

The method of any one of Embodiments 91 to 96, wherein the alkali oralkaline earth metal hydride or alkoxide is a potassium or cesiumalkoxide.

Embodiment 98

The method of any one of Embodiments 85 to 97, where the organosilane istriethylsilane and the strong base is potassium tert-butoxide.

Embodiment 99

The method of any one of Embodiments 85 to 88, wherein the organosilaneand the at least one strong base are present together at a molar ratio,with respect to one another, in a range of from about 20:1 to about 1:1.

Embodiment 100

The method of any one of Embodiments 85 to 99, wherein the at least onestrong base and substrate are present together at a molar ratio, withrespect to one another, in a range of from about 0.01:1 to about 5:1,preferably in a range of from about 0.01:1 to about 0.9:1.

Embodiment 101

The method of any one of Embodiments 85 to 100, wherein the organicsubstrate comprises an optionally substituted benzene, biphenyl,naphthalene, or anthracene ring structure.

Embodiment 102

The method of any one of Embodiments 85 to 101, wherein the organicsubstrate comprises an exocyclic aromatic C—X bond, where X is N, O, orS.

Embodiment 103

The method of any one of Embodiments 85 to 102, wherein the organicsubstrate comprises an exocyclic aromatic C—X bond and the silylationoccurs ortho to the exocyclic C—X bond, where X is N, O, or S.

Embodiment 104

The method of any one of Embodiments 85 to 103, wherein the organicsubstrate comprises a heteroaryl moiety.

Embodiment 105

The method of any one of Embodiments 85 to 104, wherein the substratecomprises an optionally substituted furan, pyrrole, thiophene, pyrazole,imidazole, triazole, isoxazole, oxazole, thiazole, isothiazole,oxadiazole, pyridine, pyridazine, pyrimidine, pyrazine, triazone,benzofuran, benzopyrrole, benzothiophene, isobenzofuran,isobenzopyrrole, isobenzothiophene, indole, isoindole, indolizine,indazole, azaindole, benzisoxazole, benzoxazole, quinoline,isoquinoline, cinnoline, quinazoline, naphthyridine,2,3-dihydrobenzofuran, 2,3-dihydrobenzopyrrole,2,3-dihydrobenzothiophene, dibenzofuran, xanthene, dibenzopyrol, ordibenzothiophene moiety.

Embodiment 106

The method of any one of Embodiments 85 to 105, wherein the substratecomprises an optionally substituted furan, pyrrole, thiophene, pyrazole,imidazole, benzofuran, benzopyrrole, benzothiophene, indole, azaindole,dibenzofuran, xanthene, dibenzopyrrole, or a dibenzothiophene.

Embodiment 107

The method of any one of Embodiments 85 to 106, wherein the organicaromatic substrate comprises at least one of the following moieties:

where X is N—R″, O, or S;

Y is H, N(R″)₂, O—R″, or S—R″

p is 0 to 4, 0 to 3, 0 to 2, or 0 to 1;

R′ is a functional group “Fn,” as described above, or (R′)_(p) is anoptionally substituted fused alicyclic, heteroalicyclic, aryl orheteroaryl moiety; and

R″ is an amine protecting group or an optionally substituted alkyl,aryl, heteroaryl, alkaryl or alk-heteroaryl, preferably optionallysubstituted C₁-C₆ alkyl, phenyl, tolyl, benzyl, or phenethyl.

Embodiment 108

The method of any one of Embodiments 85 to 107, wherein the substratecomprises at least one of the following moieties:

where X, Y, R′, R″ and p are as defined above. Note that the designation

in each case, is intended to allow for substitution on either aromaticring.

Embodiment 109

The method of any one of Embodiments 85 to 108, wherein the organicsubstrate comprises a heteroaryl moiety of structure:

and the silylation occurs at the C-2 position of the heteroaryl ring.

Embodiment 110

The method of any one of Embodiments 85 to 109, wherein the organicsubstrate comprises a heteroaryl moiety of structure:

and the silylation occurs at the C-3 position of the heteroaryl ring.

Embodiment 111

The method of any one of Embodiments 85 to 110, wherein the aromaticsubstrate comprises at least one alpha-methyl or methylene C—H bond,said method resulting in the formation of a alpha silane.

Embodiment 112

The method of any one of Embodiments 25 to 111, wherein the aromaticsubstrate is polymeric.

Embodiment 113

The method of any one of Embodiments 85 to 112, wherein the aromaticsilylated product is further reacted under conditions sufficient tocouple the silylated product with a second aromatic compound to preparea biaryl product.

Embodiment 114

The method of any one of Embodiments 85 to 112, wherein the aromaticsilylated product is further reacted under conditions sufficient toconvert the silylated product to an aromatic hydroxylated product.

Embodiment 115

The method of any one of Embodiments 85 to 112, wherein the aromaticsilylated product is further reacted under conditions sufficient toconvert the silylated product to an aromatic alpha-olefin product.

EXAMPLES

The following Examples are provided to illustrate some of the conceptsdescribed within this disclosure. While each Example is considered toprovide specific individual embodiments of composition, methods ofpreparation and use, none of the Examples should be considered to limitthe more general embodiments described herein.

In the following examples, efforts have been made to ensure accuracywith respect to numbers used (e.g. amounts, temperature, etc.) but someexperimental error and deviation should be accounted for. Unlessindicated otherwise, temperature is in degrees C., pressure is at ornear atmospheric.

Example 1: General Information

All reactions were carried out in dry glassware under an argonatmosphere using standard Schlenk line techniques or in a VacuumAtmospheres Glovebox under a nitrogen atmosphere unless specifiedotherwise. Mesitylene (puriss., ≧99.0% (GC)) was degassed by threefreeze-pump-thaw cycles prior to use. All other solvents were purifiedby passage through solvent purification columns and further degassedwith argon. Tetrahydrofuran was purified by passage through a solventpurification column then further distilled over sodium-potassium alloyand degassed with argon. All other solvents were purified by passagethrough solvent purification columns and further degassed with argon.NMR solvents for air-sensitive experiments were dried over CaH₂ andvacuum transferred or distilled into a dry Schlenk flask andsubsequently degassed with argon. Triethylsilane (99%) anddeuterotriethylsilane (97 atom % D) were purchased from Sigma-Aldrichand degassed by three freeze-pump-thaw cycles prior to use and othercommercially available liquid reagents were treated analogously.Di-4-(methyl)phenyl ether, 1-naphthol, 2-naphthol, 4-tert-butylanisole,4-methylanisole, 1,3-diphenoxybenzene, 2-methoxynaphthalene, and 1.0Mtetrabutylammonium fluoride THF solution were purchased fromSigma-Aldrich and used as received. Phenyldimethylsilane (≧98%),ethyldimethylsilane(98%) and diethylsilane (99%) were purchased fromSigma-Aldrich and distilled over CaH₂ and degassed by threefreeze-pump-thaw cycles prior to use. Other commercially availableliquid reagents were treated analogously. 1-methylindole (≧97%),benzofuran (99%), thianaphthene (98%), 1-methoxynaphthalene (≧98%),anisole (99%) and thioanisole (99%) were purchased from Sigma-Aldrichand were distilled prior to use. 2-methoxynaphthalene was recrystallizedtwice from boiling Et₂O. 1-phenylpyrrole (99%) was dissolved in Et₂O andpassed through activated alumina. The ether was removed in vacuo and thesolid residue was recrystallized twice from a 3:1 mixture of absoluteEtOH/water. 1-phenyl pyrrole (99%), diphenyl ether (≧99%),dibenzothiophene (≧99%) were purchased from Sigma-Aldrich and used asreceived. 4-methoxypyridine (97%) and 2,6-dimethoxypyridine (98%) werepurchased from Sigma-Aldrich, passed several times through neutral,activated alumina and subjected to 3 freeze-pump-thaw cycles prior touse. 1-methyl-7-azaindole was prepared following the procedure of Cheve,G. et al., Medchemcomm 2012, 3, 788. Sublimed grade KO-t-Bu (99.99%) waspurchased from Sigma-Aldrich and subjected to vacuum sublimation (30mTorr, 160° C.) prior to use. Di-4-(methyl)phenyl ether, 1-naphthol,2-naphthol, 4-tert-butylanisole, 4-methylanisole, 1,3-diphenoxybenzene,2-methoxynaphthalene, and 1.0M tetrabutylammonium fluoride THF solutionwere purchased from Sigma-Aldrich and used as received.4-(Methoxy)dibenzofuran, (2) di-4-(tert-butyl)phenyl ether (3), naphthylethers (3), 4-(phenyl)phenyl phenyl ether, 2-ethoxynaphthalene,2-Neopentyloxynaphthalene, 2-tert-butyloxynaphthalene were synthesizedaccording to the literature procedures. Standard NMR spectroscopyexperiments were conducted on a Varian Mercury (H, 300 MHz)spectrometer, a Varian Inova 400 MHz spectrometer, a Varian 500 MHzspectrometer equipped with an AutoX probe, or a Varian 600 MHzspectrometer equipped with a Triax Probe. Chemical shifts are reportedin ppm downfield from Me₄Si by using the residual solvent peak as aninternal standard. Spectra were analyzed and processed using MestReNovaVer. 7. GC-FID analyses were obtained on an Agilent 6890N gaschromatograph equipped with a HP-5 (5%-phenyl)-methylpolysiloxanecapillary column (Agilent). GC-MS analyses were obtained on an Agilent6850 gas chromatograph equipped with a HP-5(5%-phenyl)-methylpolysiloxane capillary column (Agilent).High-resolution mass spectra (EI and FAB) were acquired by theCalifornia Institute of Technology Mass Spectrometry Facility. EPRspectra were recorded on a Bruker EMS spectrometer.

Example 2: ICP-MS Analysis

ICP-MS analysis was conducted using the California Institute ofTechnology MS facility with 100 mg samples of dibenzofuran,triethylsilane, mesitylene and potassium tert-butoxide, which were addedto 50 mL DigiTUBE digestion tubes (SCP Science) followed by addition of3.0 mL of Plasma Pure nitric acid (SCP Science) to each digestion tubeand heating to 75° C. for 36 hours. After digestion, each sample wasdiluted using Nanopure/Milli Q water to 50 mL and sample analysisperformed on an HP 4500 ICPMS spectrometer. Semiquantitative analysiswas performed using a 10 ppm solution of lithium, yttrium, cerium andthallium for calibration. Each sample was analyzed twice and the averagemeasurements are given. (Table 1).

TABLE 1 ICP-MS Analysis of Various Metals in Reagents and ReactionMixture Reagent (unit: ppm) Reaction Element Dibenzofuran KOt-Bu Et₃SiHMesitylene Mixture Fe 0.15 4.92 0.67 0.11 5.80 Ru 0.00 0.07 0.00 0.013.13 Os 0.01 0.01 0.01 0.00 0.20 Co 0.00 0.01 0.00 0.00 0.26 Rh 0.000.00 0.00 0.00 1.07 Ir 0.00 0.01 0.00 0.09 0.40 Ni 0.12 0.06 0.06 0.380.79 Pd 0.00 0.04 0.00 0.01 0.88 Pt 0.00 0.07 0.00 0.01 1.74 Cu 0.0310.42 0.04 0.09 7.59

Example 3: General Procedure

In a glovebox, a 4 mL screw cap vial was loaded with the correspondingsubstrate (0.1 mmol, 1 equiv.), base (0.5-5 equiv.) and a magneticstirring bar, followed by syringe addition of the solvent (1 mL) andtriethylsilane (1-5 equiv.). The reaction vial was sealed with aTeflon-lined screw cap and heated at a given temperature and time insidethe glovebox. After cooling to room temperature, dark red to blackreaction mixture was diluted with diethyl ether (3 mL) and carefullyquenched with 1 ml of 1 N aqueous HCl. Tridecane (internal standard forGC) was added, the organic layer was separated and the aqueous layer wasextracted with ether (3 mL) until TLC controls show no UV-activecompounds present in the extracts. The combined organic layers werepassed through a short pad of Celite and subjected to GC/FID, GC/MS and¹H-NMR analyses. Unless stated otherwise, in preparative experimentsonly products with the overall yield exceeding 2% were isolated andcharacterized. In the case of naphthyl alkyl ethers, a different workupprocedure was used. After cooling, the reaction was diluted withdichloromethane (5 mL) and carefully quenched with 2 mL of 1 N aqueousHCl. Tridecane was added, and the mixture was transferred to aseparatory funnel. The organic phase was separated, and the aqueouslayer was extracted with dichloromethane (3 mL). The combined organiclayers were dried over anhydrous MgSO₄ and filtered. For all reactions,the products were identified using GC/MS and GC/FID and NMR bycomparison with the authentic samples. Trace soluble side productsobserved in naphthyl alkyl ether reductions included naphthalene,1,2,3,4-tetrahydronaphthalene, and 5,6,7,8-tetrahydro-2-naphthol.

Example 4: Synthesis and Characterization of Selected Compounds Example4.1: 4-(Triethylsilyl)Dibenzofuran (3)

The title compound was prepared by analogy to the protocol for thesynthesis of 4-(trimethylsilyl)dibenzofuran by Kelly and co-workers;Bekele, H., et al., J. Org. Chem., 1997, 62, 2259. Data for (3):Colorless oil. ¹H-NMR (500 MHz, CDCl₃): δ 7.99-7.96 (m, 2Har), 7.59(d-like, J=10 Hz, 1H_(ar)), 7.54 (dd, J=2, 5 Hz, 1H_(ar)), 7.48-7.44 (m,1H_(ar)), 7.37-7.33 (m, 2H_(ar)), 1.03 (m, 15H, 3CH₂CH₃). ¹³C-NMR (126MHz, CDCl₃) δ 161.30, 156.05, 133.57, 126.92, 122.52, 122.48, 121.58,120.68, 111.75, 7.63, 3.59. HRMS: [C₁₈H₂₂OSi] calculated 282.1440;measured 282.1444.

Example 4.2: 4,6-Bis(Triethylsilyl)Dibenzofuran (4)

To a solution of dibenzofuran (2.00 g, 11.9 mmol, 1 equiv.) andtetramethylethylenediamine (11.1 mL, 29.7 mmol, 2.5 equiv.) intetrahydrofuran (50 ml) t-butyllithium (17.5 mL of 1.7 M solution inpentane, 29.8 mmol, 2.5 equiv.) was slowly added at −78° C. under argon.The mixture was allowed to reach ambient temperature and stirring wascontinued for 4 h prior to addition of chlorotriethylsilane (10.1 mL, 60mmol, 5 equiv.). The resulting mixture was stirred at ambienttemperature for another 16 h. After quenching the reaction with thesaturated ammonium chloride solution (40 mL) and extraction with diethylether (3×30 mL), the combined organic layers were dried over anhydroussodium sulfate, filtered and the filtrate concentrated in vacuo. Crudereaction mixture was purified by chromatography on silica (hexanes) andproduct obtained was recrystallized from a mixture of methanol andisopropanol (1:1) to afford 4,6-bis(triethylsilyl)dibenzofuran (1.28 g,2.45 mmol, 28%) as colorless needles. Data for (4): Colorless needles.M.p.=59-61° C. ¹H-NMR (300 MHz, CDCl₃) δ 7.97 (dd, J=3, 9 Hz, 2H_(ar)),7.54 (dd, J=3, 9 Hz, 2H_(ar)), 7.33 (t, J=9 Hz, 2H_(ar)), 1.07-0.95 (m,30H, 6 CH₂CH₃). ¹³C-NMR (126 MHz, CDCl3) δ 160.90, 133.48, 122.87,122.34, 121.57, 120.03, 7.66, 3.52. HRMS: [C₂₄H₃₆OSi₂] calculated396.2305; measured 396.2321.

Example 4.3: 3-(Triethylsilyl)Biphenyl-2-Ol (5)

The title compound was prepared via cleavage of 3 (vide infra). Data for(5): White solid. M.p.=44-46° C. ¹H-NMR (300 MHz, CDCl₃) δ 7.52-7.40 (m,5H_(ar)), 7.36 (dd, J=3, 9 Hz, 1H_(ar)), 7.23 (dd, J=3, 6 Hz, 1H_(ar)),6.98 (t, J=9 Hz, 1H_(ar)), 5.41 (s, 1H, OH), 1.02-0.96 (m, 9H, CH₃),0.91-0.83 (m, 6H, CH₂). ¹³C-NMR (75 MHz, CDCl₃) δ 157.25, 137.51,135.97, 131.30, 129.58, 129.39, 128.01, 127.17, 123.04, 120.40, 7.79,3.69. HRMS: [C₁₈H₂₄OSi] calculated 284.1596; measured 284.1583.

Example 4.4: (3′-Triethylsilyl)Biphenyl-2-Ol (6)

The title compound was prepared via cleavage of 3 (vide infra). Data for(6): Colorless oil. ¹H-NMR (500 MHz, CDCl₃): δ 7.57-7.56 (m, 1H_(ar)),7.54-7.52 (m, 1H_(ar)), 7.49-7.44 (m, 2H_(ar)), 7.28-7.24 (m, 2H_(ar)),7.02-6.99 (m, 2H_(ar)), 5.24 (s, 1H, OH), 0.98 (t, J=10 Hz, 9H, CH₃),0.82 (q, J=15 Hz, 6H, CH₂). ¹³C NMR (126 MHz, CDCl₃): δ 153.44, 139.07,136.12, 134.71, 133.76, 130.23, 129.36, 129.08, 128.53, 128.44, 120.80,115.72, 7.43, 3.31. HRMS: [C₁₈H₂₄OSi] calculated 284.1596; measured284.1585.

Example 4.5: 3,3′-Bis(Triethylsilyl)Biphenyl-2-Ol (7)

The title compound was prepared according to General Procedure byheating dibenzofuran (1, 840 mg, 5.0 mmol, 1 equiv.) with KOt-Bu (1.12g, 10 mmol, 2 equiv.) and Et₃SiH (4.0 ml, 25 mmol, 5 equiv.) in 20 ml oftoluene for 20 hours at 100° C. After acidic aqueous work up, the crudereaction mixture was purified by chromatography on silica using hexanesand hexanes-ether (10:1) to give, among other isolated products, 20 mg(0.05 mmol, 1%) of 7. Data for (7): oily solid ¹H-NMR (300 MHz, CDCl₃):δ 7.53-7.44 (m, 2H_(ar)), 7.46-7.44 (m, 2H_(ar)), 7.36 (dd, J=1.5, 7.5Hz, 1H_(ar)), 7.23 (dd, J=1.5, 7.5 Hz, 1H_(ar)), 6.98 (t, J=7 Hz,1H_(ar)), 5.42 (s, 1H, OH), 1.01-0.96 (m, 18H, 6CH₃) 0.91-0.77 (m, 15H,6CH₂). ¹³C NMR (75 MHz, CDCl₃): δ 157.37, 139.45, 136.61, 135.87,135.09, 133.86, 131.38, 129.57, 128.71, 127.55, 122.97, 120.36, 7.80,7.57, 3.69, 3.46. HRMS: [C₂₄H₃₈OSi₂] calculated 398.2461; measured396.2470.

Example 4.6: o-Triethylsilyldiphenyl Ether

o-Triethylsilyldiphenyl ether was prepared using the modified procedureby Fink on a 30 mmol scale based on diphenyl ether. After addition ofEt₃SiCl, the reaction mixture was stirred at 40° C. for 4 hours followedby aqueous work up and vacuum distillation to obtain the title compoundas colorless oil in 88% yield. ¹H-NMR (500 MHz, CDCl₃: δ 7.47 (dd,J=7.0, 1.5 Hz, 1H_(ar)), 7.35-7.31 (m, 2H_(ar)), 7.30-7.25 (m, 1H_(ar)),7.10-7.06 (m, 1H_(ar)), 7.02-6.97 (m, 2H_(ar)), 6.79 (d, J=8.0,1H_(ar)), 0.95 (t-like, J=8.5 Hz, 9H), 0.83 (qlike, J=8.0 Hz, 6H).¹³C-NMR (126 MHz, CDCl₃: δ 162.33, 157.39, 136.57, 130.58, 129.86,129.82, 127.76, 123.34, 123.08, 122.86, 119.04, 117.22, 7.71, 3.55.HRMS: [C₁₈H₂₄SiO] calculated 284.1596, measured 284.1587.

Example 5: Selected Reactions Example 5.1: Preparative Scale Cleavage ofDibenzofuran and Deuteration Experiments

The reaction was conducted according to the General Procedure by heatingdibenzofuran (1, 250 mg, 1.49 mmol, 1 equiv.), KOt-Bu (500 mg, 4.46mmol, 3 equiv.) and Et₃SiH (713 microliters, 4.46 mmol, 3 equiv.) in 4.4mL of mesitylene for 20 hours at 165° C. After dilution with diethylether (5 mL), the organic phase was first washed with water (1 mL), andthen with 2.5N KOH solution (3×20 mL). The basic aqueous fractions werecollected and washed through once with CH₂Cl₂ (25 ml) to remove anyundesired organics. The resulting basic aqueous fractions were thenacidified with concentrated HCl until a pH of 1 and then subsequentlyextracted with CH₂Cl₂ (3×25 mL). The organic fractions were collectedand concentrated under reduced pressure to give pale yellow crystals.Purification by chromatography on silica gel with hexanes/ethyl acetate(gradient elution: 0% to 5% ethyl acetate) afforded biphenyl-2-ol (2,198 mg, 1.16 mmol, 79%) as a colorless solid. ¹H and ¹³C NMR spectralassignments of 1 were consistent with those of the authentic sample.

The identical procedure applied to the reductive cleavage ofdibenzofuran but now with Et₃SiD gave undeuterated biphenyl-2-ol with76% isolated yield. HRMS: [C₁₂H₁₀O] calculated 170.0732; measured170.0720.

Repeating the aforementioned experiment with Et₃SiH and Mes-d₁₂ gavedeuterated biphenyl-2-ol in 73% isolated yield. HRMS: [C₁₂H₄D₆O]calculated 176.1108; measured 176.1115; FWHM˜4 Da. The identicalprocedure applied to the reductive cleavage of dibenzofuran but now withEt₃SiD and Mesd₁₂ gave deuterated biphenyl-2-ol with 79% isolated yield.HRMS: [C₁₂H₄D₆O] calculated 176.1108; measured 176.1108; FWHM˜4 Da.

Very little deuterium incorporation into 2 occurred when dibenzofuranwas reacted with Et₃SiD in mesitylene at 165° C. In line with this,identical base peaks in high-resolution MS spectra of biphenyl-2-olprepared either from Et₃SiH or Et₃SiD in Mes-d₁₂ indicated that rapidH/D exchange with the solvent occurred under the reaction conditions.Interestingly, as proton, carbon and HSQC spectra of deuterated 2suggested, while all of the protons underwent partial H/D exchange, onlyfor the ortho-OH position did this process reach completion.

Example 5.2: Reactions of 4-(Triethylsilyl)Dibenzofuran

The reaction was conducted according to the General Procedure by heating4-Et3Si-dibenzofuran (3, 141 mg, 0.5 mmol, 1 equiv.), KOt-Bu (112 mg, 1mmol, 2 equiv.) and Et3SiH (401 microliters, 2.5 mmol, 5 equiv.) in 2 mlof toluene for 20 hours at 100° C. After acidic aqueous work up, thecrude reaction mixture was purified by chromatography on silica usinghexanes and hexanes-ether (10:1) to isolate 2-phenylphenol (2, 30 mg,0.177 mmol, 35%), 2-triethylsilyl-6-phenylphenol (5, 37 mg, 0.134 mmol,26%), 2-(3-triethylsilylphenyl)phenol (6, 17 mg, 0.063 mmol, 12%).Quantities of unconsumed 3 as well as products 1, 4 and 7 were obtainedusing post-chromatography GC-FID analysis of the corresponding mixedfractions.

Example 5.3: Investigation of Silylated Dibenzofurans as IntermediatesTowards C—O Bond Cleavage: Cleavage Attempts with KOt-Bu

Starting material 3 (14.1 mg, 0.05 mmol, 1 equiv.) was heated withKOt-Bu (5.6 mg or 11.2 mg, 1 or 2 equiv., respectively) in 0.8 mld-toluene at 100° C. for 20 hours in a J. Young tube under nitrogen.Monitoring the reaction progress by ¹H NMR showed no conversion of 3 inboth cases. Likewise, starting materials 3 (28.2 mg, 0.1 mmol, 1 equiv.)or 4 (39.6 mg 0.1 mmol, 1 equiv.) were heated with KOt-Bu (36.6 mg) in0.3 mL of mesitylene at 160° C. for 20 hours. Subsequent analysis of thecrude reaction mixtures by GC-FID or 1H NMR revealed 3% conversion to 1in case of 3 and 5% conversion to 3 from 4.

Example 5.4: Cleavage of 4,6-Bis(Triethylsilyl)Dibenzofuran

The reaction was conducted according to the General Procedure by heating2-(3′-triethylsilylphenyl)phenol (4, 39.6 mg, 0.1 mmol, 1 equiv.),KOt-Bu (33.6 mg, 0.3 mmol, 3 equiv.) and Et3SiH (48 microliters, 0.3mmol, 3 equiv.) in 0.2 ml of mesitylene for 20 hours at 160° C. Afteracidic aqueous work up, internal standard was added and the crudereaction mixture was analyzed by GC-FID.

Example 5.5: Reactions of 4-(Methoxy)Dibenzofuran at ElevatedTemperature

The reaction was conducted according to the General Procedure by heating4-MeO-dibenzofuran (8, 89 mg, 0.5 mmol, 1 equiv.), KOt-Bu (112 mg, 1mmol, 2 equiv.) and Et₃SiH (401 microliters, 2.5 mmol, 5 equiv.) in 2 mlof toluene for 20 hours at 100° C. After aqueous work up, the crudereaction mixture was purified by chromatography on silica using hexanesand hexanes-ether to recover unconsumed starting material 8 (3 mg, 0.015mmol, 3%) and isolate dibenzofuran (1, 8.4 mg, 0.05 mmol, 10%; sincefractions of 1 contained small amounts of starting 8, quantification wasdone by ¹H-NMR with CH₂Br₂ as an internal standard), 1,1′-biphenyl-2-ol(2, 4.3 mg, 0.025 mmol, 5%), 4-Et₃Si-dibenzofuran (3, 11 mg, 0.039 mmol,8%), 2-methoxy-6-phenyl-phenol (9, mg, 0.025 mmol, 5%),2-(3′-methoxyphenyl)phenol (10, 47 mg, 0.235 mmol, 47%). Note: onlycompounds with the yield exceeding 2% were characterized. ¹H and ¹³C NMRspectral assignments of 9 and 10 were consistent with literaturereports.

Example 5.6: Synthesis of 4,6-Di(Methyl)Dibenzofuran

To a solution of dibenzofuran (2.00 g, 11.9 mmol, 1 equiv.) andtetramethylethylenediamine (11.1 mL, 29.7 mmol, 2.5 equiv.) in diethylether (50 ml) t-butyllithium (17.5 mL of 1.7 M solution in pentane, 29.8mmol, 2.5 equiv.) was slowly added at minus 78° C. under argon. Themixture was allowed to reach ambient temperature and stirring wascontinued for 4 h prior to addition of methyl iodide (3.7 mL, 60 mmol, 5equiv.). The resulting mixture was stirred at ambient temperature foranother 16 h. After quenching the reaction with the saturated ammoniumchloride solution (40 mL) and extraction with diethyl ether (3×30 mL),the combined organic layers were dried over anhydrous sodium sulfate,filtered and the filtrate concentrated in vacuo. Crude reaction mixturewas purified by chromatography on silica (hexanes) and product obtainedwas recrystallized from methanol to afford 4,6-dimethyldibenzofuran (480mg, 2.45 mmol, 21%) as a colorless solid. Data for (15): 1H-NMR (300MHz, CDCl₃): δ 7.75 (dd, J=1.0, 6.0 Hz, 2H_(ar)), 7.24-7.20 (m,4H_(ar)), 2.61 (s, 6H, 2CH₃). ¹³C NMR (75 MHz, CDCl₃): δ 155.07, 128.00,124.17, 122.60, 122.02, 118.2, 15.41. HRMS: [C₁₄H₁₂O] calculated196.0888; measured 196.0884.

Example 5.7: Cleavage of 4,6-Di(Methyl)Dibenzofuran

The reaction was conducted according to the General Procedure by heating4,6-di(methyl)dibenzofuran (15, 98 mg, 0.5 mmol, 1 equiv.), KOt-Bu (112mg, 1 mmol, 2 equiv.) and Et₃SiH (401 microliters, 2.5 mmol, 5 equiv.)in 2 ml of toluene for 20 hours at 100° C. After aqueous work up, thecrude reaction mixture was purified by chromatography on silica usinghexanes-ether 4:1 to obtain 77 mg of product 16 as yellow oil. Data for(16): ¹H-NMR (500 MHz, CDCl₃): δ 7.35 (t, J=7.5 Hz, 1H_(ar)), 7.25-7.22(m, 2H_(ar)), 7.20-7.18 (m, 1H_(ar)), 7.11 (d-like, J=10 Hz, 1H_(ar)),7.05 (d-like, J=7.5 Hz, 1H_(ar)), 6.87 (t, J=7.5 Hz 1H_(ar)), 5.31 (s,1H, OH), 2.39 (s, 3H, CH₃), 2.30 (s, 3H, CH₃). ¹³C-NMR (126 MHz, CDCl₃):δ 150.68, 139.26, 137.36, 130.51, 129.93, 129.39, 128.73, 127.83,127.76, 126.20, 124.70, 120.25, 21.60, 16.33. HRMS: [C₁₄H₁₄O] calculated198.1045, measured 198.1046.

Repeating this experiment in mesitylene, at 165° C. for 20 hoursresulted in 100% conversion of the starting material 15, with 96% yieldof 16.

While comprehensive mechanistic studies are still required before theunderlying reaction pathways can be reliably established, havingobserved no conversion of 3 (4-(Triethylsilyl)dibenzofuran) under basicconditions and smooth reductive cleavage of 4,6-dimethyldibenzofuran 15into the corresponding biphenyl-2-ol 16, the intermediacy of benzynes,as the presence of ortho-silylated aromatic ethers might have initiallysuggested, seems unlikely.

Example 5.8: EPR Experiments

Dibenzofuran (1, 16.8 mg, 0.1 mmol, 1 equiv.), KOt-Bu (22.5 mg, 0.2mmol, 2 equiv.) and Et₃SiH (80 microliters, 0.5 mmol, 5 equiv.) wereheated in 0.4 ml of toluene for 1 hour at 100° C. inside the glovebox.After this time reaction mixture was diluted with 0.8 ml of toluene andfiltered into an EPR tube. The reaction mixture was found to be EPRactive and the spectrum was recorded within 20 min after filtration(FIG. 2). In a control experiment recorded without dibenzofuran, thesame signal was observed albeit with lower intensity. These results areconsistent with reactive radicals that have been documented forhomolytic aromatic substitution reactions. The addition of1,10-phenanthroline in conjunction with KOt-Bu was found to bedetrimental since no conversion of 1 was observed.

Example 5.9: Optimization Details for the Cleavage of Dibenzofuran

Experiments were conducted using the General Methods described inExamples 1 and 3, unless otherwise indicated. Yields were reproduciblewithin ±2%. It is noteworthy here that low levels of base, especiallysubstoichiometric amounts of base relative to the substrate, even atthese elevated temperatures, resulted in the highest yields of silylatedproducts, relative to cleavage products.

TABLE 2 Results of optimization for cleavage of dibenzofuran

Et₃SiH Base Conv Entry (equiv) (equiv) Solvent T, ° C. (%)^(a) 2 3 4 5 67  1 0 KOt-Bu Toluene 100 0 — — — — — — (2)  2 5 None Toluene 100 0 — —— — — —  3^(a) 5 KOt-Bu Toluene 100 70 34 28 4 — — — (2)  4^(b) 5 KOt-BuToluene 100 98 38 16 10 21 2 7 (2)  5^(c) 5 KOt-Bu Toluene 100 98 5 2846 — — — (2)  6 4 KOt-Bu Toluene 100 100 41 17 15 12 1 9 (2)  7 3 KOt-BuToluene 100 96 42 20 9 13 1 4 (2)  8 2 KOt-Bu Toluene 100 87 34 30 10 61 3 (2)  9 1 KOt-Bu Toluene 100 56 19 29 1 2 — 1 (2) 10 5 KOt-Bu Toluene100 89 12 48 20 9 — 1 (0.5) 11 2 KOt-Bu Toluene 100 66 9 43 8 2 — — (5)12 3 KOt-Bu Toluene 100 97 63 10 1 22 — 2 (2) 13 5 KH (1) Dioxane 100 491 43 5 — — — 14 5 KOt-Bu Dioxane 100 70 25 28 10 4 1 1 (2) 15^(d) —KOt-Bu Et₃SiH 100 99 26 13 25 11 1 21 (2) 16 5 KOt-Bu Toluene 80 98 2918 26 9 — 7 (2) 17 3 KOt-Bu Mesitylene 165 100 85 3 — 5 2 — (3) 18^(e) 3KOt-Bu Mesitylene 165 100 95 — — — — — (3) 19 2 KOt-Bu Mesitylene 165100 62 8 1 12 1 — (2) 20 3 KOt-Bu Mesitylene 165 97 52 17 5 16 1 2 (2)21 1 KOt-Bu Mesitylene 165 57 30 21 — — — — (1) 22 3 KOt-Bu Mesitylene165 85 29 35 15 4 — 2 (0.5) 23 5 KOt-Bu Mesitylene 165 100 77 3 0 3 8 —(5) 24 3 KH (3) Mesitylene 165 100 66 3 0 5 11 — 25 3 KOEt Mesitylene165 100 85 4 0 1 8 — (3) 26 3 KOEt Mesitylene 165 95 77 10 11 — — — (3)27 3 KOEt Toluene 100 40 19 19 2 — — — (3) 28 3 KOMe Mesitylene 165 6431 27 2 3 1 — (3) 29 3 NaOt-Bu Mesitylene 165 0 — — — — — — (3) 30 3LiOt-Bu Mesitylene 165 0 — — — — — — (3) 31 3 NaOEt Mesitylene 165 0 — —— — — — (3) 32^(f) 3 CsOR Toluene 100 89 75 3 11 — — — (2) 33 3 KOt-BuBenzene 85 96 37 20 13 12 — 9 (3) 34 5 KOt-Bu DMF 100 0 — — — — — — (2)35 5 KOt-Bu DMA 100 0 — — — — — — (2) 36 5 KOt-Bu Diglyme 100 0 — — — —— — (2) 37 5 KOt-Bu t-BuOH 100 0 — — — — — — (2) 38 5 KOt-Bu Diisopropyl100 0 — — — — — — (2) carbonol 39 3 KOt-Bu Methyl 160 100 82 — — 13 (3)cyclohexane 40^(g) PMHS KOt-Bu Methyl 85 5-7 — — — — — — (10) (3)cyclohexane ^(a)GC yields and conversions are reported using tridecaneas the standard ^(b)the reaction was performed in 0.05 M solution.^(c)reaction conducted open to an Ar line ^(d)the reaction was performedin neat Et₃SiH. ^(e)with 1,4-cyclohexadiene (100 equivalent) co-solvent^(f)R = 2-ethylhexyl. ^(g)using polymethylhydrosiloxane (PMHS) insteadof Et₃SiH as organosilane

Example 5.10: Reductive Cleavage of Diaryl Ethers

In order to explore the cleavage of aryl ether C—O bonds in unstrainedsubstrates and probe if it proceeds without undesired overreduction ofthe resulting aromatic fragments, diphenyl ether was subjected to theadditives-free optimized reaction conditions described above. Thissubstrate provided benzene and phenol in moderate yields (Table 3,Entry 1) with the rest of the mass balance being attributed principallyto silylated as well as other unidentified products. With this result inhand, the reactivity of more complex diaryl ethers was evaluated. Bothsymmetrical and unsymmetrical diaryl ethers were shown to be competentsubstrates and underwent C—O cleavage with good to excellentefficiencies (Entries 2-7). Many of the evaluated diaryl ethers provedmore reactive as compared to diphenyl ether and allowed for the use ofmilder reaction conditions. In the case of 1-naphthyl phenyl ether(Entry 5), bond cleavage occurred regiospecifically at the naphthyl C—Obond to furnish naphthalene and phenol in 70% and 91% yieldrespectively, with no 1-naphthol or benzene detected. With theunsymmetrical dinaphthyl ether (Entry 5), C—O bond reduction occurredregioselectively to provide 2-naphthol and 1-naphthol in good combinedyield with approximately a 4:1 ratio of the two isomers, respectively.The unsymmetrical para-phenyl substituted diphenyl ether (Entry 7)reacts with good overall yield and with moderate regioselectivity forreduction of the slightly more electron rich C—O bond indicating theapparent influence of electronic effects in site selectivity of C—O bondcleavage. This factor becomes determining for the selectivity ofcleavage of 4-O-5 lignin models that contain strong methoxy donorsadjacent to the C—O bond being broken (vide infra, Scheme 2). Suchselectivity is complementary to that reported by other for homogeneousNi catalyzed reduction with dihydrogen wherein unsymmetrical diarylethers were preferentially cleaved at the side of the moreelectron-deficient aryl ring.

TABLE 3 Reductive cleavage of diaryl ethers^(a)

Entry Diaryl ether Conv. (%)

1 

 96 64 65 2 

100 76 98 3 

100 52 84 4^(b)

100 50 88 5^(c)

100 — 70 91 — 6^(d)

100 57 58 15 7^(d)

100 41 19 21 65 ^(a)GC yields and conversions are reported usingtridecane as a standard. ^(b)Trace amount of1,2,3,4-tetrahydronaphthalene was detected. ^(c)Reaction was run at 100°C. for 20 h in toluene with 2 equiv. each of Et₃SiH and KOt-Bu.^(d)Reaction was run at 75° C. for 40 h in toluene.

Example 5.11: Reductive Cleavage and Silylations of Aryl Alkyl Ethers

Reductions and silylations of aryl alkyl ethers were conducted under theoptimized conditions applied to diaryl ethers to probe the cleavageselectivity of sp2 versus sp3 C—O bond. The reaction of2-methoxynaphthalene gave 2-naphthol as the major product in moderateyield (Scheme 1). GC-MS analysis of the crude reaction mixture indicatedthe presence of trace amounts of naphthalene along with2-methylnaphthalene and further reduced species, including products ofpartial aromatic reduction. Compounds presumably derived from 2-naphtholsilylation were also detected. Likewise, cleavage of 2-ethoxynapthaleneunder the same conditions gave 2-naphthol in slightly higher yield, butwith the same or analogous side products. Sterically bulkier ethers wereinvestigated to probe the versatility and possible mechanism of the C—Obond cleavage. Despite the large alkyl substituent adjacent to the etheroxygen, reaction of 2-neopentyloxynaphthalene provided 2-naphthol inapproximately the same yield as with the less bulky substrates. Even2-tert-butyloxynapthalene was cleaved to give the expected naphthol in55% yield (Scheme 1). Control experiments performed at identicalconditions but without triethylsilane provided 2-naphthol in cases of2-ethoxy- and 2-tert-butyloxynapthalene albeit with substantiallydiminished yields. Since 2-methoxy- and 2-neopentyloxy-substratesremained intact in such silane-free cleavages, a b elimination mechanismis likely to be operative. When attempting to reduce 4-tert-butyl and4-methyl anisoles under the standard conditions, the yields of thecorresponding phenols were high, likely because of more challengingsilylation of the substituted phenyl ring for the steric reasons (Scheme2).

Overall, the selectivity for alkyl C—O bond scission contrasts with thatobserved in Ni- and borane catalyzed C—O cleavage reactions where arylC—O reduction occurs. It is also notable that under these conditionsonly trace amounts of naphthalene ring hydrogenation products wereobserved, which contrasts with the results of silane-based ionichydrogenations reported in the literature.

It is instructive to compare the cleavages of methoxysubstituted diary′ethers 8 and 11 (Scheme 2) with the results presented above. While arylalkyl ethers showed strong preference for the reduction of alkyl oxygenover aryl oxygen bonds, both methoxy substrates in Scheme 2 demonstrateda reversal of regioselectivity, furnishing almost exclusively aryloxygen bond rupture products. While not intending to be bound by thecorrectness of this theory, this effect may be attributed to thepresence of a donor oxygen atom ortho to the C—O bond undergoingrupture. Supporting this inference is the high selectivity of thereductive ring-opening of dibenzofuran derivative 8 that mainly leads to10. Likewise, preferred formation of phenol and anisole was observedwith similar selectivity over phenols 12 and 13 in the cleavage oflignin model 11. One may speculate, without being bound to thecorrectness of the theory, that such an effect can be rationalized bythe oxygen atom resonance stabilization of the positive charge build upduring electrophilic activation of the C—O bond that is being broken. Inorder to test this hypothesis, compound 3 was subject to the reactionconditions and isolated the ring opened phenols 5 and 6 along with thedesilylated products 1 and 2 (Scheme 2, inset C). In the absence ofresonance stabilization, the selectivity of cleavage was reversed infavor of isomer 5. It is also worth noting that, as formation of 1 and 2demonstrated, the silylation reaction was thus reversible under thetypical reaction conditions. After having illustrated the potential forthe challenging 4-O-5 lignin models 8 and 11, this method was testedwith an oligomeric ether 14 that contains six C_(ar)-0 bonds (Scheme 2,inset D). Remarkably, at 165° C. in mesitylene quantitative conversionof 14 was achieved and gave phenol, benzene, resorcinol and otherunidentified products with merely 0.5 equivalent of silane per aryloxygen bond.

In Scheme 2, compounds 1 to 7 refer to the corresponding compoundsdescribed in Example 5.9.

Example 5.12: Experiments as to the Effects of Certain Additives on theCleavage of Dibenzofuran

In additional experiments, the reactivity of Et₃SiH was tested in thepresence of various additives so as to attempt to elucidate a mechanismfor the reaction, The results are shown in the following Table 4. Noneof products 2-7 were identified.

TABLE 4 Effects of additives on the cleavage of dibenzofuran ConversionEntry Et₃SiH (equiv) Base (equiv) Additive Solvent T, ° C. (%) 1 5KOt-Bu (2) 1,10-phen^(a) Toluene 100 5 (2) 2 5 KOt-Bu (2) 18-crown-6Toluene 100 0 (2.5) 3 3 — KBH₄ (3) Mesitylene 165 0 4 3 — KCN (3)Mesitylene 165 0 5 3 — DIBAL^(b) (3) Mesitylene 165 0 6 3 — LiAlH₄ (3)Mesitylene 165 0 7 3 — Bu₃SnH (3) Mesitylene 165 0 8 5 — Me₄NF (2)Toluene 100 0 9 5 — Bu₄NF (2) Toluene 100 0 10 — KOt-Bu (2) KH (2)Dioxane 100 0 ^(a)1,10-phen is 1,10-phenanthroline. ^(b)DIBAL isDiisobutylaluminium hydride

Example 5.13: Experiments with Benzyl Ethers

Experiments were conducted on benzylic ethers using the GeneralProcedures described in Example 3. Surprisingly, the methods were shownto be capable of inducing complete deoxygenation of these lignin modelsubstrates. This type of reactivity appears to be unprecedented in thestate-of-the-art homogeneous systems, even at elevated temperatures.

Example 5.14: Experiments with C—N and C—S Heteroaryl Compounds

Experiments were also conducted with C—N and C—S heteroaryl compounds.In the case of compounds comprising C—N bonds, reactivity appeared to besimilar to that seen for C—O bonds, and it is reasonably expected thatthe wide ranging methods used for the latter would result in similarreactivity in the former:

In the case of compounds comprising C—S compounds, the methods appear togenerally result in complete desulfurization of the molecules. Thisdifference in reactivities may reflect the differences in bond energiesbetween the C—O, C—N, and C—S bonds (compare C—X bond dissociationenergies in phenol (111), aniline (104), and thiophenol (85, all inkcal/mol). Of particular interest was the desulfurization of evenhindered dibenzothiophenes under relatively mild conditions. In none ofthese conversions were single C—S products detected:

Example 6. Exemplary Silylation Reactions Example 6.1:Triethylsilylation of Arenes at Elevated Temperatures

In many instances the formation of the solvent-derived silylatedproducts was observed at elevated temperatures during experiments aimedat C—O, C—N, or C—S bond cleavage when using toluene or mesitylene assolvents at the elevated temperatures used in the reductive cleavagereactions. Since it was not possible to separate the resulting productsfrom their respective parent solvents by column chromatography ordistillation, at this point it was difficult to assess their yields, butthey are tentatively estimated to be in 5-10% range based on Et₃SiH. Incase of toluene, the identity of products was confirmed by comparison ofthe NMR spectra obtained with the literature data (Rychnovsky, et al. J.Org. Chem. 2003, 68, 10135.) Thus, it was concluded that the majorproduct is benzyl triethylsilane (17), which is also consistent with theGC-MS analysis of fragmentation patterns of isomeric products. Likewise,it appeared that silylation of mesitylene proceeds predominantly intothe benzylic (or alpha) position. HRMS [C₁₅H₂₆Si] calculated 234.1804,measured 234.1804).

Aromatic amines are also amenable to silylation. In the following case,GC-MS identified the following scheme was operable under the conditionsprovided:

At lower temperatures, this reaction appeared to provide a mixture ofproduct, with no single product identifiable. It is possible, though notconfirmed, that the apparent normal proclivity to silylate ortho to theexocyclic amine was inhibited by the steric bulk associated with the twomethyl groups.

Example 6.2: Silylation of Aryl Alkyl Ethers and Thioethers at AmbientTemperatures Example 6.2.1: Triethyl(2-Methoxyphenyl)Silane

The reaction was conducted according to the General Procedure by heatinganisole (54 mg, 0.5 mmol, 1 equiv.), KOt-Bu (11 mg, 0.1 mmol, 0.2 equiv)and Et₃SiH (239 microliters, 1.5 mmol, 3 equiv.) in 1 mL oftetrahydrofuran for 65 hours at 65° C. After aqueous work up, the crudereaction mixture was purified by chromatography on silica using hexanes(isochratic) to obtain 59 mg (54%) of the title compound as a colourlessoil. ¹H NMR (500 MHz, THF-d8) δ 7.40-7.17 (m, 2H), 7.01-6.81 (m, 2H),3.77 (s, 3H), 1.02-0.85 (m, 9H), 0.87-0.74 (m, 6H). ¹³C NMR (126 MHz,THF-d8) δ 164.58, 135.52, 130.42, 123.92, 120.08, 109.23, 54.09, 6.93,3.22.

Example 6.2.2: Triethyl(3-Methoxynaphthalen-2-Yl)Silane

The reaction was conducted according to the General Procedure by heating2-methoxynaphthalene (79 mg, 0.5 mmol, 1 equiv.), KOt-Bu (19.6 mg, 0.18mmol, 0.35 equiv.) and Et₃SiH (319 microliters, 2.0 mmol, 4 equiv.) in 1mL of tetrahydrofuran for 48 hours at 65° C. After aqueous work up, thecrude reaction mixture was purified by chromatography on silica elutingwith hexanes (isochratic) to obtain 79 mg (58%) of the title compound ascolourless oil. ¹H NMR (500 MHz, THF-d8) δ 7.84 (s, 1H), 7.78-7.73 (d,1H), 7.73-7.68 (d, 1H), 7.38 (ddd, J=8.2, 6.8, 1.3 Hz, 1H), 7.27 (ddd,J=8.1, 6.8, 1.2 Hz, 1H), 7.15 (s, 1H), 3.90 (s, 3H), 1.01-0.90 (m, 9H),0.68-0.53 (m, 6H). ¹³C NMR (126 MHz, THF-d₈) δ 163.03, 137.88, 136.83,130.10, 128.58, 128.09, 127.29, 127.21, 124.03, 104.57, 55.25, 8.02,7.48. HRMS: [C₁₇H₂₄OSi] calculated 272.1608, measured 272.1596. The HSQCspectra of the 2-methoxynaphthalene and its reaction product areprovided in FIG. 7.

Interestingly, the reaction starting with 1-methoxynaphthalene did notresult in silylated product:

The reaction was conducted according to the General Procedure by heating1-methoxynaphthalene (79 mg, 0.5 mmol, 1 equiv.), KOt-Bu (11.2 mg, 0.1mmol, 0.1 equiv) and Et₃SiH (240 microliters, 1.5 mmol, 3 equiv.) in 1mL of tetrahydrofuran for 65 hours at 65° C. The reaction was dilutedwith diethyl ether (1 mL), quenched with water (0.5 mL) and the organicphase was analyzed by GC-MS, GC-FID and 1H NMR analysis. Analysis byGC-MS and GC-FID (tridecane standard) revealed the formation of aryl C—Ocleavage product naphthalene and alkyl C—O bond cleavage productnaphthol in 13 and 8 percent yield respectively, notably to the completeexclusion of any silylated species.

Example 6.2.3 Silylation of Diphenyl Ether

The reaction was conducted according to the General Procedure by heatingphenyl ether (85 mg, 0.5 mmol, 1 equiv.), KOt-Bu (11 mg, 0.10 mmol, 0.2equiv) and Et₂SiH₂ (194 microliters, 1.5 mmol, 3 equiv.) in 1 mL oftetrahydrofuran for 65 hours at 65° C. After aqueous work up, the crudereaction mixture was purified by chromatography on silica using an 80:2mixture of hexanes:triethylamine to obtain 68 mg (20%) of the titlecompound as a colourless oily solid. ¹H NMR (500 MHz, THF-d₈) δ7.64-7.57 (m, 2H), 7.55 (dd, J=7.3, 1.8 Hz, 1H), 7.41 (ddd, J=8.3, 7.2,1.8 Hz, 1H), 7.15 (dd, J=8.3, 1.0 Hz, 1H), 7.14-7.09 (m, 2H), 4.34(Si—H) (p-like, J=1.2 Hz, 1H), 1.06-0.95 (m, 12H), 0.92-0.82 (m, 8H).¹³C NMR (126 MHz, THF-d₈) δ 166.04, 161.43, 139.74, 137.00, 135.55,135.05, 132.12, 130.19, 128.79, 123.56, 123.37, 118.41, 9.06, 7.93,6.70, 4.83. HRMS: [C₂₀H₂₇OSi₂] calculated 339.1601, measured 339.1607

A second fraction of the reaction mixture yielded 34 mg (39%) of thecyclized derivative. ¹H NMR (500 MHz, THF-d₈) δ 7.57-7.50 (m, 2H), 7.40(ddd, J=8.3, 7.2, 1.8 Hz, 2H), 7.15 (dd, J=8.6, 0.7 Hz, 2H), 7.11 (td,J=7.2, 1.0 Hz, 2H), 0.99-0.95 (m, 4H), 0.92-0.86 (m, 6H). ¹³C NMR (126MHz, THF-d₈) δ 161.54, 134.96, 132.07, 123.41, 118.80, 117.39, 7.95,6.72. HRMS: [C₁₆H₁₉OSi] calculated 255.1205, measured 255.1206. The HSQCspectra of these reaction products are provided in FIGS. 8A and 8B.

A third fraction was obtained, containing a product in low yield (ca.7%) whose spectral characteristics appear to be consistent with thestructure of the monosilylated product shown above.

Example 6.2.4: Triethyl((Phenylthio)Methyl)Silane

The reaction was conducted according to the General Procedure by heatingthioanisole (62 mg, 0.5 mmol, 1 equiv.), KOt-Bu (11 mg, 0.1 mmol, 0.2equiv) and Et₃SiH (239 microliters, 1.5 mmol, 3 equiv.) in 1 mL oftetrahydrofuran for 65 hours at 65° C. After aqueous work up, the crudereaction mixture was purified by chromatography on silica using hexanes(isochratic) to obtain 81 mg (68%) of the title compound as a colourlessoil. ¹H NMR (500 MHz, THF-d8) δ 7.31-7.26 (m, 2H), 7.25-7.19 (m, 2H),7.11-7.01 (m, 1H), 1.03 (t, J=7.9 Hz, 9H), 0.78-0.60 (m, 6H). ¹³C NMR(126 MHz, THF-d8) δ 140.73, 128.31, 125.69, 124.19, 13.01, 6.62, 3.06.HRMS: [C₁₃H₂₁SSi] calculated 237.1140, measured 237.1133. The HSQCspectra of the thioanisole and its reaction product as provided in FIGS.9A and 9B.

Example 6.3: Experiments with Heteroaryl Compounds at AmbientTemperatures

A series of experiments were done at ambient (65° C. or below) to testthe regioselectivity of several of the more reactive heteroarylcompounds. The test conditions and results are shown below. Yields forall reactions are either by isolation (chromatography on silica gel, orbul-to-bulb distillation) or by GC-FID or NMR analysis using internalstandard for quantification. Note that C-3 silylated heteroarenes werefound in some cases to be prone to protodelilylation on silica gel. Inthese cases, bulb-to-bulb distillation was used or, alternatively,silica gel chromatography with ca. 3% triethyl amine added to theeluent, or a combination of both methods. Products were identified asindicated by interpreting available ¹H, ¹³C NMR, and HeteronuclearSingle Quantum Coherence (HSQC) spectroscopy, or GC-MS, or a combinationof these methods, where possible using comparisons with authenticsamples.

Example 6.3.1: 1-Methyl-2-(Triethylsilyl)-1H-Indole

The reaction was conducted according to the General Procedure by heatingN-methylindole (66 mg, 0.5 mmol, 1 equiv.), KOt-Bu (8.4 mg, 0.08 mmol,0.15 equiv.) and Et₃SiH (239 microliters, 1.5 mmol, 3 equiv.) in 1 mL oftetrahydrofuran for 48 hours at 23° C. After aqueous work up, the crudereaction mixture was purified by chromatography on silica eluting withhexanes (isochratic) to obtain 88 mg (72%) of the title compound as acolourless oil. ¹H NMR (500 MHz, THF-d8) δ 7.50 (dt, J=7.9, 1.0 Hz, 1H),7.32 (dq, J=8.3, 0.9 Hz, 1H), 7.11 (ddd, J=8.2, 6.9, 1.2 Hz, 1H), 6.97(ddd, J=7.9, 7.0, 0.9 Hz, 1H), 6.68 (d, J=0.9 Hz, 1H), 3.84 (s, 3H),1.06-0.98 (m, 9H), 0.98-0.92 (m, 6H). ¹³C NMR (126 MHz, THF-d8) δ140.48, 136.86, 128.70, 121.44, 120.05, 118.51, 112.96, 108.71, 32.18,6.83, 3.63. The structural characterization of this reaction product isbased, in part, on an interpretation of the HSQC spectrum of thisreaction product as provided in FIG. 10.

Example 6.3.2: 1-Methyl-3-(Triethylsilyl)-1H-Indole

The reaction was conducted according to the General Procedure by heatingN-methylindole (66 mg, 0.5 mmol, 1 equiv.), KOt-Bu (56 mg, 0.5 mmol, 1equiv.) and Et₃SiH (88 microliters, 0.55 mmol, 1.1 equiv.) in 1 mL oftetrahydrofuran for 312 hours at 23° C. After aqueous work up, the crudereaction mixture was purified by chromatography on silica eluting with95:5 hexanes:NEt₃ (isochratic) to obtain 103 mg (84%) of the titlecompound as a colourless oil. ¹H NMR (500 MHz, THF-d8) δ 7.63 (dt,J=7.9, 1.0 Hz, 1H), 7.32 (dt, J=8.2, 0.9 Hz, 1H), 7.15 (s, 1H), 7.12(ddd, J=8.2, 7.0, 1.1 Hz, 1H), 7.01 (ddd, J=8.0, 7.0, 1.1 Hz, 1H), 3.78(s, 3H), 1.06-0.95 (m, 9H), 0.95-0.83 (m, 6H). ¹³C NMR (126 MHz, THF-d8)δ 138.63, 135.94, 133.37, 121.44, 120.88, 118.79, 108.96, 104.39, 31.61,7.04, 4.11. The structural characterization of this reaction product isbased, in part, on an interpretation of the HSQC spectrum of thisreaction product as provided in FIG. 11.

Example 6.3.3: 2-(Ethyldimethylsilyl)-1-Methyl-1H-Indole

The reaction was conducted according to the General Procedure by heatingN-methylindole (62 mg, 0.5 mmol, 1 equiv.), KOt-Bu (11 mg, 0.1 mmol, 0.2equiv) and EtMe₂SiH (198 microliters, 1.5 mmol, 3 equiv.) in 1 mL oftetrahydrofuran for 48 hours at 23° C. After aqueous work up, the crudereaction mixture was purified by chromatography on silica using hexanes(isochratic) to obtain 80 mg (74%) of the title compound as a colourlessoil. ¹H NMR (500 MHz, THF-d8) δ 7.48 (d, J=7.9 Hz, 1H), 7.31 (dd, J=8.4,1.0 Hz, 1H), 7.10 (ddd, J=8.2, 6.9, 1.2 Hz, 1H), 6.95 (ddd, J=7.9, 6.9,0.9 Hz, 1H), 6.64 (d, J=0.9 Hz, 1H), 3.84 (s, 3H), 1.05-0.95 (m, 3H),0.89 (d, J=7.9 Hz, 2H), 0.38 (s, 6H). ¹³C NMR (126 MHz, THF-d8) δ140.45, 138.94, 128.58, 121.45, 120.10, 118.51, 113.53, 111.90, 108.67,32.17, 7.37, 6.77, −3.67. HRMS: [C₁₃H₁₉NSi] calculated 217.1280;measured 217.1287.

Example 6.3.4: 1-Benzyl-2-(Triethylsilyl)-1H-Indole

The reaction was conducted according to the General Procedure by heating1-benzylindole (62 mg, 0.5 mmol, 1 equiv.), KOt-Bu (11 mg, 0.1 mmol, 0.2equiv) and and Et₃SiH (239 microliters, 1.5 mmol, 3 equiv.) in 1 mL oftetrahydrofuran for 48 hours at 23° C. After aqueous work up, the crudereaction mixture was purified by chromatography on silica using hexanes(isochratic) to obtain 50 mg (31%) of the title compound as a colourlessoily solid. ¹H NMR (500 MHz, THF-d8) δ 7.56 (ddd, J=7.7, 1.3, 0.7 Hz,1H), 7.25-7.07 (m, 4H), 7.02 (ddd, J=8.2, 6.9, 1.3 Hz, 1H), 6.98 (ddd,J=7.9, 6.9, 1.1 Hz, 1H), 6.92-6.86 (m, 2H), 6.80 (d, J=0.9 Hz, 1H), 5.52(s, 2H), 1.06-0.88 (m, 9H), 0.85-0.69 (m, 6H).

Example 6.3.5: 1-Benzyl-2-(Ethyldimethylsilyl)-1H-Indole

The reaction was conducted according to the General Procedure by heating1-benzylindole (104 mg, 0.5 mmol, 1 equiv.), KOt-Bu (17 mg, 0.15 mmol,0.3 equiv) and EtMe₂SiH (198 microliters, 1.5 mmol, 3 equiv.) in 1 mL oftetrahydrofuran for 65 hours at 25° C. After aqueous work up, the crudereaction mixture was purified by chromatography on silica using an80:1:4 mixture of hexanes:diethyl ether:triethylamine respectively toobtain 107 mg (73%) of the title compound as a colourless oil. ¹H NMR(500 MHz, THF-d₈) δ 7.55 (ddd, J=7.7, 1.4, 0.8 Hz, 1H), 7.22-7.16 (m,2H), 7.16-7.09 (m, 2H), 7.02 (ddd, J=8.2, 6.9, 1.4 Hz, 1H), 6.97 (ddd,J=8.0, 6.9, 1.2 Hz, 1H), 6.86 (ddd, J=7.2, 1.3, 0.7 Hz, 2H), 6.78 (d,J=0.9 Hz, 1H), 5.51 (d, J=1.1 Hz, 2H), 0.95-0.90 (m, 3H), 0.24 (s, 6H).¹³C NMR (126 MHz, THF-d8) δ 141.31, 140.50, 139.94, 130.09, 129.39,127.90, 126.71, 122.96, 121.45, 120.10, 113.93, 110.81, 50.62, 8.50,7.93, −2.40. HRMS: [C₁₉H₂₃NSi] calculated 293.1600, measured 293.1590.

Example 6.3.6: 1-methyl-2-(triethylsilyl)-1H-pyrrolo[2,3-b]pyridine

The reaction was conducted according to the General Procedure by heatingN-methyl-1H-pyrrolo[2,3-b]pyridine (66 mg, 0.5 mmol, 1 equiv.), KOt-Bu(11 mg, 0.1 mmol, 0.2 equiv.) and Et₃SiH (239 microliters, 1.5 mmol, 3equiv.) in 1 mL of tetrahydrofuran for 45 hours at 35° C. After aqueouswork up, the crude reaction mixture was purified by chromatography onsilica using step gradient elution (starting with 100% hexanes andincreasing the polarity of the eluent stepwise to 30% EtOAc in Hexanes)to obtain 89 mg (73%) of the title compound as a pale yellow oil. ¹H NMR(500 MHz, THF-d8) δ 8.45-7.95 (m, 1H), 7.97-7.66 (m, 1H), 6.95 (dd,J=7.7, 4.6 Hz, 1H), 6.68 (s, 1H), 3.94 (s, 2H), 1.05-1.00 (m, 9H), 0.97(td, J=7.1, 1.7 Hz, 6H). ¹³C NMR (126 MHz, THF-d8) δ 150.95, 142.87,137.82, 127.38, 120.13, 114.79, 110.76, 30.27, 6.74, 3.31. HRMS:[C₁₄H₂₃N₂Si] calculated 247.1642, measured 247.1631. The structuralcharacterization of this reaction product is based, in part, on aninterpretation of the HSQC spectrum of this reaction product as providedin FIG. 12.

Example 6.3.7: Silylation of N-methyl-2-methylindole

The reaction was conducted according to the General Procedure by heating1,2-dimethylindole (73 mg, 0.5 mmol, 1 equiv.), KOt-Bu (17 mg, 0.15mmol, 0.3 equiv) and Et₃SiH (319 microliters, 2.0 mmol, 4 equiv.) in 1mL of tetrahydrofuran for 65 hours at 65° C. After aqueous work up, thecrude reaction mixture was purified by chromatography on silica using an80:1:4 mixture of hexanes:diethyl ether:triethylamine respectively toobtain 74 mg (57%) of the title compound as a colourless oil. ¹H NMR(500 MHz, THF-d₈) δ 7.35-7.29 (m, 1H), 7.19 (dd, J=8.1, 0.9 Hz, 1H),6.97 (ddd, J=8.2, 7.1, 1.2 Hz, 1H), 6.90 (ddd, J=8.0, 7.1, 1.1 Hz, 1H),6.06 (d, J=0.8 Hz, 1H), 3.64 (s, 3H), 2.25 (d, J=0.7 Hz, 2H), 0.96 (t,J=7.9 Hz, 9H), 0.71-0.58 (m, 6H). ¹³C NMR (126 MHz, THF-d₈) δ 139.50,138.30, 129.69, 120.24, 119.70, 119.47, 109.27, 98.96, 29.75, 11.73,7.62, 4.16. HRMS: [C₁₆H₂₅NSi] calculated 259.1756, measured 259.1754.The structural characterization of this reaction product is based, inpart, on an interpretation of the HSQC spectrum of this reaction productas provided in FIG. 13.

Example 6.3.8: Silylation of N-Methyl Pyrrole

Example 6.3.9: 9,9-Diethyl-9H-Benzo[d]Pyrrolo[1,2-a][1,3] Azasilole

The reaction was conducted according to the General Procedure by heating1-phenylpyrrole (161 mg, 0.5 mmol, 1 equiv.), KOt-Bu (11 mg, 0.1 mmol,0.2 equiv) and Et₂SiH₂ (194 microliters, 1.5 mmol, 3 equiv.) in 1 mL oftetrahydrofuran for 65 hours at 60° C. After aqueous work up, the crudereaction mixture was purified by chromatography on silica using hexanes(isochratic) to obtain 97 mg (85%) of a mixture containing approximatelya 7:1 mixture of the title compound and the starting material as acolourless oily solid. ¹H NMR (500 MHz, THF-d8) δ 7.51 (ddd, J=7.1, 1.5,0.6 Hz, 1H), 7.47 (dd, J=2.6, 1.1 Hz, 1H), 7.43-7.39 (m, 1H), 7.38-7.33(m, 1H), 7.04 (td, J=7.2, 1.0 Hz, 1H), 6.45 (dd, J=3.2, 1.1 Hz, 1H),6.29 (t, J=2.9 Hz, 1H), 1.00-0.94 (m, 6H), 0.94-0.86 (m, 4H). ¹³C NMR(126 MHz, THF-d₈) δ 134.81, 131.71, 130.28, 124.66, 120.80, 118.47,118.18, 114.05, 112.42, 111.28, 7.91, 5.18. HRMS: [C₁₄H₁₈NSi] calculated228.1213, measured 228.1208. The structural characterization of thisreaction product is based, in part, on an interpretation of the HSQCspectrum of this reaction product as provided in FIG. 14.

Example 6.3.10: Benzofuran-2-Yltriethylsilane

The reaction was conducted according to the General Procedure by heatingbenzofuran (59 mg, 0.5 mmol, 1 equiv.), KOt-Bu (19.6 mg, 0.18 mmol, 0.35equiv.) and Et₃SiH (239 microliters, 1.5 mmol, 3 equiv.) in 1 mL oftetrahydrofuran for 45 hours at 60° C. After aqueous work up, the crudereaction mixture was purified by chromatography on silica eluting withhexanes (isochratic) to obtain 44 mg (38%) of the title compound as acolourless oil. ¹H NMR (500 MHz, Acetone-d6) δ 7.64 (ddd, J=7.7, 1.3,0.7 Hz, 1H), 7.53 (dd, J=8.2, 0.9 Hz, 1H), 7.30 (ddd, J=8.3, 7.2, 1.3Hz, 1H), 7.22 (ddd, J=7.7, 7.2, 1.0 Hz, 1H), 7.16 (d, J=1.0 Hz, 1H),1.09-0.98 (m, 9H), 0.92-0.84 (m, 6H). The structural characterization ofthis reaction product is based, in part, on an interpretation of theHSQC spectrum of this reaction product as provided in FIG. 15.

Example 6.3.11: Benzo[b]thiophen-2-yldimethyl(phenyl)silane

The reaction was conducted according to the General Procedure by heatingthianaphthene (66 mg, 0.5 mmol, 1 equiv.), KOt-Bu (8.4 mg, 0.08 mmol,0.15 equiv.) and Et₃SiH (239 microliters, 1.5 mmol, 3 equiv.) in 1 mL oftetrahydrofuran for 50 hours at 23° C. After aqueous work up, the crudereaction mixture was purified by chromatography on silica eluting with80:2 hexanes:triethylamine to obtain 103 mg (83%) of the title compoundas a colourless oil. ¹H NMR (500 MHz, THF-d8) δ 7.90-7.85 (m, 1H),7.84-7.76 (m, 1H), 7.53 (d, J=0.8 Hz, 1H), 7.34-7.20 (m, 2H), 1.08-0.99(m, 9H), 0.95-0.80 (m, 6H). ¹³C NMR (126 MHz, THF-d8) δ 144.78, 142.34,139.12, 132.97, 125.10, 124.84, 124.34, 122.91, 7.84, 5.10. HRMS:[C₁₄H₂₀SSi] calculated 248.1051, measured 248.1055. The structuralcharacterization of this reaction product is based, in part, on aninterpretation of the HSQC spectrum of this reaction product as providedin FIG. 16(B).

Example 6.3.12: Benzo[b]thiophen-2-yldimethyl(phenyl)silane

The reaction was conducted according to the General Procedure by heatingthianaphthene (66 mg, 0.5 mmol, 1 equiv.), KOt-Bu (8.4 mg, 0.08 mmol,0.15 equiv.) and PhMe₂SiH (239 microliters, 1.5 mmol, 3 equiv.) in 1 mLof tetrahydrofuran for 48 hours at 65° C. After aqueous work up, thecrude reaction mixture was purified by chromatography on silica elutingwith hexanes (isochratic) to obtain 102 mg (76%) of the title compoundas a pale yellow oily solid. ¹H NMR (500 MHz, CDCl₃) δ 7.94-7.87 (m,1H), 7.85-7.78 (m, 1H), 7.71-7.58 (m, 2H), 7.51 (d, J=0.8 Hz, 1H),7.46-7.39 (m, 3H), 7.38-7.30 (m, 2H), 0.69 (s, 6H). NMR (126 MHz, CDCl₃)δ 144.01, 141.12, 140.18, 137.29, 134.13, 132.41, 129.70, 128.09,124.45, 124.18, 123.69, 122.33, −1.42. HRMS: [C₁₆H₁₆SSi] calculated268.0743, measured 268.0742

Example 6.3.13: Silylation of Dibenzothiophene

The reaction was conducted according to the General Procedure by heatingdibenzothiophene (92 mg, 0.5 mmol, 1 equiv.), KOt-Bu (5.6 mg, 0.05 mmol,0.1 equiv) and Et₃SiH (160 microliters, 1.0 mmol, 2 equiv.) in 1 mL of1,4-dioxane for 14 hours at 75° C. After aqueous work up, the crudereaction mixture was purified by chromatography on silica using an 80:2mixture of hexanes:triethylamine to obtain 51 mg (34%) of the titlecompound as a colourless oil. ¹H NMR (500 MHz, THF-d₈) δ 8.26-8.22 (m,2H), 7.90-7.86 (m, 1H), 7.59 (dd, J=7.1, 1.3 Hz, 1H), 7.47-7.41 (m, 3H),1.11-1.02 (m, 6H), 1.02-0.95 (m, 9H). ¹³C NMR (126 MHz, THF-d₈) δ146.49, 140.15, 136.57, 136.06, 134.74, 131.79, 127.63, 125.30, 124.86,123.53, 123.39, 122.48, 7.94, 3.98. HRMS: [C₁₈H₂₂SSi] calculated255.1205, measured 255.1206, The structural characterization of thisreaction product is based, in part, on an interpretation of the HSQCspectrum of this reaction product as provided in FIG. 17.

Example 6.3.14: Silylation of 2,5-Dimethyl Thiophene

The reaction was conducted according to the General Procedure by heating2,5, dimethyl thiophene (56 mg, 0.5 mmol, 1 equiv.), KOt-Bu (11.2 mg,0.1 mmol, 0.2 equiv.) and Et₃SiH (3 equiv.) in tetrahydrofuran for 45hours at 65° C. GC-MS of the crude product mixture yielded a mass peakassociated with the monosilated derivative. ¹H NMR data were consistentwith formation of 2-methyl-5-(triethylsilylmethyl)thiophene. ¹H NMR (500MHz, THF-d8) δ 6.52-6.42 (m, 1H), 6.41-6.29 (m, 1H), 2.35 (s, 3H), 2.23(s, 2H), 1.00-0.92 (m, 9H), 0.63-0.53 (m, 6H). ¹³C NMR (126 MHz, THF-d8)δ 140.78, 136.28, 125.96, 124.03, 15.73, 15.45, 7.97, 4.08. HRMS:[C₁₂H₂₂SSi] calculated 226.1212, measured 226.1220

Example 6.3.15: Silylation of Pyridine

The reaction was conducted according to the General Procedure by heatingpyridine (40 mg, 0.5 mmol, 1 equiv.), KOt-Bu (17 mg, 0.15 mmol, 0.3equiv) and Et₃SiH (240 microliters, 1.5 mmol, 3 equiv.) in 1 mL oftetrahydrofuran for 65 hours at 65° C. After aqueous work up, the crudereaction mixture was purified by chromatography on silica using an80:1:4 mixture of hexanes:diethyl ether:triethylamine respectively toobtain 14 mg (15%) of the title compound as a colourless oily solid. ¹HNMR (500 MHz, THF-d₈) δ 8.99-8.16 (m, 2H), 7.62-7.07 (m, 2H), 1.01-0.93(m, 6H), 0.91-0.79 (m, 4H). ¹³C NMR (126 MHz, THF-d₈) δ 149.88, 129.76,129.29, 7.70, 3.66. HRMS: [C₁₁H₂₀NSi] calculated 194.1365, measured194.1367

Example 6.3.16: Attempted Silylation of 4-Methoxypyridine

The reaction was conducted according to the General Procedure by heating4-methoxypyridine (55 mg, 0.5 mmol, 1 equiv.), KOt-Bu (17 mg, 0.15 mmol,0.3 equiv) and Et₃SiH (240 microliters, 1.5 mmol, 3 equiv.) in 1 mL oftetrahydrofuran for 65 hours at 65° C. The reaction was diluted withdiethyl ether (1 mL), quenched with water (0.5 mL) and the organic phasewas analyzed by GC-MS, GC-FID and 1H NMR analysis and revealed noapparent conversion of the starting material to silylated products.

Example 6.3.17: Attempted Silylation of 2,6 Dimethoxypyridine

The reaction was conducted according to the General Procedure by heating2,6-dimethoxypyridine (70 mg, 0.5 mmol, 1 equiv.), KOt-Bu (17 mg, 0.15mmol, 0.3 equiv) and Et₃SiH (240 microliters, 1.5 mmol, 3 equiv.) in 1mL of tetrahydrofuran for 65 hours at 65° C. The reaction was dilutedwith diethyl ether (1 mL), quenched with water (0.5 mL) and the organicphase was analyzed by GC-MS, GC-FID and 1H NMR analysis. GC-MS analysisrevealed major mass peaks corresponding to the formation of 2 silylatedproduct isomers as well as several unidentified products.

Example 7. Evaluation of Basic Activators in Silylation Reactions

The effects of various bases were evaluated under the following nominalconditions, with the results provided in Table 3:

TABLE 3 Effect of bases on the silylation of N-methyl indole at ambientconditions Base Yield C2 (%) Selectivity KOtBu 66.7 >95% DABCO 0 — KHMDS44 >95% LiOtBu 0 — NaOtBu 0 — Na0Et 0 — KOEt 14.2 >95% NaOAc 0 — KOAc 0— KOMe 4.6 >95% Cs₂CO₃ 0 — KH 0.1 — KOH 0 — TBAF 0 — KF 0 — CsF 0 — NaF0 — Me₄NF 0 — KOtBu + 18-crown-6 0 — (1:1) Yields and selectivitiescalculated using GC-FID analysis with mesitylene added as a standard forquantification. C2 selectivity defined as (yield C2 product)/(yield C2 +C3 product) × 100%

As can be seen from Table 3, typical silicon activators such as fluoridesalts are not competent in catalyzing the reactions described herein.TBAF, KF, CsF, Me₄NF, NaF all give no conversion of the substrate.

Interestingly, while KOR salts appear to be excellent catalysts for thesilylation transformation (with KOtBu being superior to all others, andwith efficiency of other potassium alkoxides correlating loosely withbasicity), NaOR and LiOR where R is Me, Et, iPr, tBu all give 0%conversion. This demonstrates the critical, albeit unknown, role of thepotassium cation in this reaction.

Notably, the addition of 18-crown-6 as a potassium chelator in anequimolar amount to KOtBu gives 0% conversion of the substrate understandard conditions, thus lending further support for a critical role ofthe potassium cation. Interestingly, other potential chelants did notinhibit, and in many cases, improved both yield and selectivity of thesystems. This effect is not well understood. Without being bound by thecorrectness of this or any other theory, it is possible that theseligands chelated the potassium cation is proposed. Bipyridine-basedligand scaffolds as well as TMEDA (not shown) were demonstrated to bemost effective in promoting high selectivity and efficiency in thesilylation reaction. This is supported by the reaction with 1,7-phen,which is unable to chelate potassium, giving a lower product yield.

TABLE 4 Effect of bases on the silylation of N-methyl indole at ambientconditions Ligand Yield C2 Selectivity 1,10-phenanthroline 20.7 >95%1,7-phenanthroline 11.4 >95% bathophenanthroline 33.7 >95% bipyridine64.8 >95% 4,4′-di-t-Bu bipyridine 60 >95% Yields and selectivitiescalculated using GC-FID analysis with mesitylene added as a standard forquantification. C2 selectivity defined as yield (C2 product/yield C2 +C3 products) × 100%.

The activity of the inventive systems and methods were remarkablytolerant of different base loadings. In the N-methylindole model system,for example, decreasing base loading only mildly decreased efficiency.Remarkably, KOtBu even down to 1 mol % was effective and gave the majorC2 product in 65% yield and a corresponding 89% C2 selectivity. Thisloading is even lower or equal to that required for the state-of-the-arttransition-metal-based aromatic C—H silylation systems.

As those skilled in the art will appreciate, numerous modifications andvariations of the present invention are possible in light of theseteachings, and all such are contemplated hereby. For example, inaddition to the embodiments described herein, the present inventioncontemplates and claims those inventions resulting from the combinationof features of the invention cited herein and those of the cited priorart references which complement the features of the present invention.Similarly, it will be appreciated that any described material, feature,or article may be used in combination with any other material, feature,or article, and such combinations are considered within the scope ofthis invention.

The disclosures of each patent, patent application, and publicationcited or described in this document are hereby incorporated herein byreference, each in its entirety, for all purposes.

What is claimed:
 1. A method comprising contacting an aromatic organicsubstrate comprising at least one C—O, C—N, or C—S bond with acomposition comprising (a) at least one organosilane; (b) at least onestrong base; and (c) optionally at least one molecular hydrogen donorcompound, molecular hydrogen, or both, under conditions sufficient toreduce the at least one C—O, C—N, or C—S bond of the aromatic organicsubstrate or to silylate the aromatic organic substrate, such that thecontacting results in the formation of: (i) a product in which the atleast one C—O, C—N, or C—S bond of the aromatic organic substrate hasbeen reduced, or (ii) a product in which the aromatic organic substratehas been silylated, where the silylated organic substrate has acarbon-silicon bond in a position corresponding to a position on thearomatic organic substrate having a carbon-hydrogen bond, or (iii) acombination of both (i) and (ii).
 2. The method of claim 1, wherein theconditions are sufficient to reduce the at least one C—O, C—N, or C—Sbond of the aromatic organic substrate, and the product is one in whichthe at least one C—O, C—N, or C—S bond of the organic substrate has beenreduced.
 3. The method of claim 2, wherein the composition furthercomprises at least one molecular hydrogen donor compound.
 4. The methodof claim 2, wherein the aromatic organic substrate comprises at leastone C—O bond, and optionally at least one C—N bond, C—S bond, or bothC—N and C—S bonds.
 5. The method of claim 2, wherein the aromaticorganic substrate comprises at least one C—N bond, and optionally atleast one C—O bond, C—S bond, or both C—O and C—S bonds.
 6. The methodof claim 2, wherein the aromatic organic substrate comprises at leastone C—S bond, and optionally at least one C—O bond, C—N bond, or bothC—O and C—N bonds.
 7. The method of claim 2, wherein the compositionfurther comprises molecular hydrogen.
 8. The method of claim 2, whereinthe at least one C—O, C—N, or C—S bond is an aromatic C—O, C—N, or C—Sbond.
 9. The method of claim 2, wherein the at least one C—O, C—N, orC—S bond is exocyclic to an aromatic ring moiety of the aromatic organicsubstrate.
 10. The method of claim 2, wherein at least one of the atleast one C—O, C—N, or C—S bonds is endocyclic to an aromatic ringmoiety of the aromatic organic substrate.
 11. The method of claim 1,wherein the aromatic organic substrate comprises an optionallysubstituted phenyl ether, phenyl amine, phenyl sulfide, naphthyl ether,naphthyl amine, or naphthyl sulfide moiety, or combination thereof. 12.The method of claim 2, wherein the aromatic organic substrate comprisesa furan, pyrrole, thiophene, 2,3-dihydrobenzofuran, xanthene,2,3-dihydrobenzopyrrole, or 2,3-dihydrobenzothiophene moiety.
 13. Themethod of claim 1, wherein the at least one C—O, C—N, or C—S bond is analiphatic C—O, C—N, or C—S bond.
 14. The method of claim 1, that issubstantially free of water, oxygen, or both water and oxygen.
 15. Themethod of claim 1, wherein at least one organosilane comprises anorganosilane of Formula (I) or Formula (II):(R)_(4-m)Si(H)_(m)  (I)R—[—SiH(R)—O—]_(n)—R  (II) where m is 1, 2, or 3; n is 10 to 100; and Ris independently optionally substituted C₁₋₁₂ alkyl, C₁₋₁₂ heteroalkyl,C₆₋₂₀ aryl, C₅₋₂₀ heteroaryl, C₇₋₃₀ alkaryl, C₆₋₃₀ heteroalkaryl, C₇₋₃₀aralkyl, C₆₋₃₀ heteroaralkyl, —O—C₁₋₁₂ alkyl, —O—C₁₋₁₂heteroalkyl,—O—C₆₋₂₀ aryl, —O—C₅₋₂₀ heteroaryl, —O—C₇₋₃₀ alkaryl,—O—C₆₋₃₀heteroalkaryl, —O—C₇₋₃₀ aralkyl, or —O—C₆₋₃₀ heteroaralkyl, and,if substituted, the substituents may be phosphonato, phosphoryl,phosphanyl, phosphino, sulfonato, C₁-C₂₀ alkylsulfanyl, C₆-C₂₀arylsulfanyl, C₁-C₂₀ alkyl sulfonyl, C₆-C₂₀ aryl sulfonyl, C₁-C₂₀alkylsulfinyl, C₆-C₂₀ arylsulfinyl, sulfonamido, amino, amido, imino,nitro, nitroso, hydroxyl, C₁-C₂₀ alkoxy, C₆-C₂₀ aryloxy,C₂-C₂₀alkoxycarbonyl, C₆-C₂₀ aryloxycarbonyl, carboxyl, carboxyl,carboxylato, mercapto, formyl, C₁-C₂₀ thioester, cyano, cyanato,thiocyanato, isocyanate, thioisocyanate, carbamoyl, epoxy, styrenyl,silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl, or halogen, or ametal-containing or metalloid-containing group, where the metalloid isSn or Ge, or where the substituents optionally provide a tether to aninsoluble or sparingly soluble support media comprising alumina, silica,or carbon.
 16. The method of claim 15, wherein the at least oneorganosilane is (R)₃SiH, where R is C₁₋₆ alkyl.
 17. The method of claim2, wherein the at least one strong base comprises an alkali metalhydride or alkoxide.
 18. The method of claim 2, wherein the at least onestrong base comprises an alkali metal hydride.
 19. The method of claim18, wherein the at least one strong base comprises potassium hydride.20. The method of claim 2, wherein the at least one strong basecomprises an alkali metal alkoxide.
 21. The method of claim 20, whereinthe alkali metal alkoxide comprises a C₁₋₁₂ linear or branched alkylmoiety or a C₆₋₁₀ aryl or C₅₋₁₀ heteroaryl moiety.
 22. The method ofclaim 21, wherein the alkali metal alkoxide comprises methoxide,ethoxide, propoxide, butoxide, or 2-ethyl-hexyl alkoxide.
 23. The methodof claim 17, wherein the alkali metal hydride or alkoxide base is apotassium alkoxide or cesium alkoxide.
 24. The method of claim 2, wherethe at least one strong base is potassium t-butoxide.
 25. The method ofclaim 2, wherein the at least one organosilane and the at least onestrong base are present together at a molar ratio, with respect to oneanother, in a range of from about 20:1 to about 1:2.
 26. The method ofclaim 2, wherein the at least one organosilane and at least one C—O,C—N, and C—S bond in the substrate are present in a ratio of from about1:2 to about 10:1.
 27. The method of claim 2, wherein the at least onestrong base and at least one C—O, C—N, and C—S bond in the substrate arepresent in a range of from about 1:2 to about 10:1.
 28. The method ofclaim 2, wherein the at least one organosilane is present in sufficientquantity to act as a solvent for the composition.
 29. The method ofclaim 2, further comprising an organic solvent.
 30. The method of claim29, said organic solvent having a boiling point at one atmospherepressure in a range of from about 25° C. to about 450° C.
 31. The methodof claim 1, said method comprising heating the aromatic organicsubstrate and composition to a temperature in a range of from about 25°C. to about 450° C.
 32. The method of claim 1, wherein the method isconducted in the absence of added transition metal catalysts.
 33. Themethod of claim 3, wherein the at least one molecular hydrogen donorcompound comprises 1,3-cyclohexadiene, 1,4-cyclohexadiene,1,2-cyclohexadiene, 1,4-cyclohexadiene 1,2-dihydronaphthalene,1,4-dihydronaphthalene, 1,2-dihydroquinoline, 3,4-dihydroquinoline,9,10-dihydroanthracene, or tetralin.
 34. The method of claim 2, whereinthe aromatic organic substrate is contained within a biomass, biomassliquefaction, biopyrolysis oil, black liquor, coal, coal liquefaction,natural gas, or petroleum batch or process stream.
 35. The method ofclaim 2, wherein said method is conducted within a biomass, biomassliquefaction, biopyrolysis oil, black liquor, coal, coal liquefaction,natural gas, or petroleum batch or process stream.
 36. The method ofclaim 2, wherein the method produces a product in which the at least oneC—O, C—N, or C—S bond is reduced in an amount ranging from about 40% to100%, relative to the amount originally present in the substratecompound.
 37. The method of claim 1, wherein the conditions aresufficient to silylate the aromatic organic substrate, and the productis one in which the aromatic organic substrate has been silylated. 38.The method of claim 1, wherein the method comprises contacting anaromatic organic substrate comprising at least one C—O, C—N, or C—S bondwith a composition consisting essentially of: (a) an organosilane; (b) astrong base; and (c) optionally a molecular hydrogen donor compound,molecular hydrogen, or both, under conditions sufficient to reduce theat least one C—O, C—N, or C—S bond of the aromatic organic substrate orto silylate the aromatic organic substrate, such that the contactingresults in the formation of: (i) a product in which the at least oneC—O, C—N, or C—S bonds of the aromatic organic substrate has beenreduced; (ii) a product in which the organic substrate has beensilylated, where the silylated organic substrate has a carbon-siliconbond in a position corresponding to a position on the aromatic organicsubstrate having a carbon-hydrogen bond; or (iii) a combination of both(i) and (ii).
 39. The method of claim 38, wherein the conditions aresufficient to reduce at least one of the C—O, C—N, or C—S bonds of thearomatic organic substrate, and the aromatic organic substrate comprisesan optionally substituted phenyl ether, phenyl amine, phenyl sulfide,naphthyl ether, naphthyl amine, or naphthyl sulfide moiety.
 40. Themethod of claim 38, wherein the conditions are sufficient to reduce atleast one C—O, C—N, or C—S bond of the aromatic organic substrate, andthe product is one in which the at least one C—O, C—N, or C—S bond ofthe aromatic organic substrate has been reduced.
 41. The method of claim38, wherein the conditions are sufficient to silylate the aromaticorganic substrate, and the product is one in which the aromatic organicsubstrate has been silylated.
 42. The method of claim 38, wherein thearomatic organic substrate comprises lignin.
 43. The method of claim 38,wherein the organic substrate comprises a furan, pyrrole, thiophene,2,3-dihydrobenzofuran, 2,3-dihydrobenzopyrrole,2,3-dihydrobenzothiophene, or xanthene moiety.
 44. The method of claim38, wherein the organic substrate comprises an N-alkyl pyrrole, N-arylpyrrole, benzofuran, benzopyrrole, benzothiophene, dibenzofuran,dibenzopyrol, or dibenzothiophene moiety.
 45. The method of claim 38,wherein the strong base is potassium tert-butoxide.
 46. The method ofclaim 2, wherein the aromatic organic substrate comprises at least oneC—S bond and the method results in the desulfurization of the aromaticorganic substrate.
 47. The method of claim 2, wherein the aromaticorganic substrate comprises lignin.
 48. The method of claim 2, whereinthe method is conducted in the absence of added transition metalcatalysts.